Flow balancing devices, methods, and systems

ABSTRACT

The disclosed subject matter relates to extracorporeal blood processing or other processing of fluids. Volumetric fluid balance, a required element of many such processes, may be achieved with multiple pumps or other proportioning or balancing devices which are to some extent independent of each other. This need may arise in treatments that involve multiple fluids. Safe and secure mechanisms to ensure fluid balance in such systems are described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation of U.S. application Ser. No.15/517,928, filed Apr. 7, 2017, which is a U.S. national stage filingunder 35 U.S.C. § 371 of International Application No. PCT/US2015/055031filed Oct. 9, 2015, which claims the benefit of U.S. ProvisionalApplication Nos. 62/152,057 filed Apr. 24, 2015 and 62/062,764 filedOct. 10, 2014, all of which are hereby incorporated by reference intheir entireties.

STATEMENT OF GOVERNMENT SUPPORT

This invention was made with government support under HR0011-13-C-0023awarded by Defense Advanced Research Projects Agency (DARPA). Thegovernment has certain rights in the invention.

BACKGROUND

A function of some extra corporeal blood treatment systems (ECBTsystems), including hemodialysis, hemofiltration, hemodiafiltration,apheresis systems, etc., is the maintenance of the overall fluid balancebetween the fluid added to the patient and the fluid withdrawn from thepatient. Ideally, this exchange will result in a net loss or gain offluid to/from the patient that precisely matches the patient's treatmentrequirement. To achieve this, the ECBT may employ a volumetric fluidbalancing system, of which a variety of different types are known. Forexample, see U.S. Pat. Nos. 5,836,908, 4,728,433, 5,344,568, 4,894,150,and 6,284,131, each of which is hereby incorporated by reference as iffully set forth in their entireties herein.

Fluid balancing mechanisms generally attempt to ensure that the totalmass or volume of fluid pumped into, and removed from, the non-bloodside of a filter or dialysis are equal. To provide for a desireddifferential between the net quantity removed/added, the inflow andoutflow rates can be controlled to produce a net difference. This may beprovided by regulating the rates of ingoing and outgoing pumps or byusing a separate bypass, driven by a separate pump. In an example, sucha bypass pump pumps at an ultrafiltration (“UF”) line rate which isadded to the balanced withdrawal rate.

Gravimetric systems that balance flow by weighing mass from a source andcollected fluid from the treatment device and comparing the two areknown. Another approach is to measure incremental volume transfer. Hardplumbed or disposable lined balance chambers alternately fill and emptyin a manner that assures equal and opposite volume exchange. Systemsusing this approach are balancing a single inlet fluid flow with aneffluent stream. A second stream of fluid is frequently added to theextracorporeal circuit using an additional pump, or external IV pump.The volume of this second stream may be balanced by the isolatedultrafiltration (UF) pump in an attempt to maintain patient fluidbalance. This approach is limited by the calibration inaccuracies of theadditional or external pump and the isolated UF pump. These inaccuraciesare acceptable at low flow rates. However, at higher flow rates thecumulative volumetric inaccuracies may not achieve the desired patientvolumetric balance. Additionally, this approach requires an operator toindependently set the pump rates to achieve the desired balance.

SUMMARY

The disclosed subject matter described in this disclosure is analternate approach to volumetric fluid balance using multiple pumps tocontrol inflows and outflows from an extracorporeal circuit that havecorresponding pump rates synchronized and calibrated relative to eachother to assure balanced flow rates.

In certain systems, volumetric fluid balancing may be performed for asingle therapy fluid stream using a system configuration includingbalance chambers, peristaltic pumps, and mechanically controlled pinchvalves. The therapy fluid entering the blood path of the extracorporealcircuit may be balanced with effluent removed from the blood paththrough the dialyzer of the circuit so that the patient volume is notaffected by this exchange of fluids. The limitation to a single therapyfluid inlet flow is a common limitation of various dialysis machinesthat use balance chambers. Some extracorporeal therapies can use morethan one therapy fluid inlet flow that may be volumetrically controlledto achieve an overall patient fluid balance. For example, the differencebetween the total fluid that moves into the patient (for example, byflowing into the patient's blood stream) and that withdrawn from thepatient must be precisely controlled. For example, in dialysistreatment, the amount of fluid entering the patient, for example throughpredilution, post-dilution, citrate infusion, and reverseultrafiltration streams may be balanced against the net ultrafiltrationstream to achieve a target net ultrafiltration rate. The subject matterdescribed in this disclosure provides alternate machine configurationsthat support one or more therapy fluid flows synchronized with theeffluent fluid flow from the extracorporeal circuit to achieve accuratefluid balance.

The disclosed subject matter includes several different systemconfigurations that support one or more therapy fluid inlet flowsbalanced with the effluent flow by diverting each therapy flow pumpindividually using a valving/flow diversion means from their normalconfiguration during therapy and connecting the therapy fluid flow pumpoutlet in series with the effluent flow pump inlet with a pressuresensor between the therapy and effluent pumps. This calibration isachieved by synchronizing the pump flows and using the pressure sensorto synchronize the rates. A controller connected to the pressure sensorand pumps adjusts the effluent flow pump to the desired flow rate andthe selected therapy fluid flow pump to achieve a desired pressurebetween the pumps and holds the pressure stable for a period of time toachieve a synchronization flow value for the therapy fluid pump. Thiscan be repeated for multiple pressure values and stabilization times toachieve a synchronization curve for the therapy fluid flow pump versuspressure. Calibration may be performed at multiple flow rates as well toenhance the calibration algorithm. The therapy fluid flow pump is thendiverted back to its normal therapy configuration. Additional therapyfluid flows can be calibrated one at a time with the effluent fluid flowin a similar manner, or, as discussed, therapy fluid flows can becombined and synchronized together.

Once calibrated, the pumps may operate at different speeds relative toeach other to achieve the desired fluid balance outcome in theextracorporeal circuit (neutral, positive, or negative balance).

Additionally, the pump rates may be further compensated to account fortransient effects such as changes in inlet/outlet pressures, changes dueto pump life, and other factors. A compliant accumulator can be used toreduce pressure spikes and aid in achieving stable pressure controlduring the synchronization process. In the first configuration (FIGS.2A-2D), a system is shown where fluid flows are controlled by multiplepumps that are synchronized and calibrated using a compliance chamberpressure sensor. Multiple inlet flows are capable of supplying one ormore independent inlet fluids to the extracorporeal circuit. There is asingle effluent pump that will operate at a rate equal to the sum of thecombined inlet flows plus additional net ultrafiltration if desired.

Control valves are arranged so that the inlet flows can be divertedthrough a bypass fluid path either independently or in combination.Simultaneously, a control valve closes the flow of effluent from thefilter so the effluent pump is fed by the bypass fluid path. The bypassfluid path has a pressure sensor and may have a small compliance chamberto measure pressure. The bypass fluid path can be defined by fluidchannels that already form part of a circuit used for other purposessuch as blood treatment or it can be predefined part of the circuit thatis used exclusively for the purpose of connecting pumps to besynchronized. If the combined (coupled inlet and outflow pump flows)inflows match the outflow, the pressure will remain unchanged signalingthat the pumps are synchronized and calibrated. If the pressure iseither increasing or decreasing, the controller may increase or decreasepump rates to achieve balanced flow. The pressure at which the pumps aresynchronized can be varied and the flow rates at which the pumps aresynchronized can be varied, providing a comprehensive pump controlalgorithm. As disclosed flow measurement may be used for synchronizationof pumps as well.

At the beginning of a treatment and periodically throughout thetreatment, flows are diverted so that pump synchronization andcalibration may be completed.

All pumps may be equipped with inlet and may also be fitted with outletpressure sensors to support pressure compensation of the pump rate. Thatis, the flow rate of the pump may be derived from the pump rotation orreciprocation rate as adjusted by head pressure. This derivation andcompensation may be done using a single function of both head pressure(inlet, outlet, or pressure change) and rotation speed. For example thefunction may be embodied in a look up table stored in a data store of acontroller. Additionally, the control valves may be closed so that pumpocclusion may be confirmed by the reading of the various pressuresensors.

The principles of the subject matter disclosed herein are applicable toboth peristaltic pumps with disposable fluid pathways as well as hardplumbed systems and the various combinations of the two. In a hardplumbed configuration, the flow path components would requiredisinfection similar to standard dialysis machines and would requirespecial techniques to meet the requirements for direct infusion oftherapy fluids.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a generic control valve that can flow fluid in to aselected fluid line, according to embodiments of the disclosed subjectmatter.

FIG. 1B shows a type of control valve that is beneficial in disposablecircuits in which permanent clamping members open and control tubingbranches by pinching, such that the tubing branches can be hermeticallysealed and permanently connected by an inexpensive branch, according toembodiments of the disclosed subject matter.

FIG. 1C illustrates a controller that may be present in all theembodiments described herein and assumed to be present in alldescriptions of a controller, the figure showing elements connected to,or subsumed within one or more controllers that perform the one or morecontrol or computational functions described in connection with theembodiments.

FIG. 2A is a schematic diagram of an extracorporeal blood treatmentsystem, for example, a dialysis system in which an additional infusionstream is provided and balanced against an effluent stream, according toembodiments of the disclosed subject matter.

FIG. 2B is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from a firstsource is diverted directly through a branch line to the effluent outputto permit the calibration, or confirmation of calibration of a pumpingrate of fluid from the first source, to be obtained, according toembodiments of the disclosed subject matter.

FIG. 2C is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from a secondsource is diverted directly through a branch line to the effluent outputto permit the calibration, or confirmation of calibration of a pumpingrate of fluid from the second source, to be obtained, according toembodiments of the disclosed subject matter.

FIG. 2D is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from the first andsecond sources are diverted directly through branch lines to theeffluent output to permit the calibration, or confirmation ofcalibration of a pumping rate for the combined fluids flow from thefirst and second sources, to be obtained, according to embodiments ofthe disclosed subject matter.

FIG. 3A is a schematic diagram of a further extracorporeal bloodtreatment system, for example, a dialysis system, in which multipleadditional infusion streams are provided and balanced against aneffluent stream, according to embodiments of the disclosed subjectmatter.

FIG. 3B is a schematic diagram of the extracorporeal blood treatmentsystem of FIG. 3A, in a configuration in which a flow is established topermit a controller to compare the indication of a flow sensor of aselected ingoing stream to that of a flow sensor of an effluent stream,according to embodiments of the disclosed subject matter.

FIG. 3C is a schematic diagram of the extracorporeal blood treatmentsystem of FIG. 3A, in a configuration in which a flow is established topermit a controller to compare the indication of multiple flow sensorsof multiple ingoing streams to that of a flow sensor of an effluentstream, according to embodiments of the disclosed subject matter.

FIG. 4A shows a volumetric balancing system of an extracorporeal bloodtreatment system with a secondary flow that is selectively connectablein a push pull relationship with an ultrafiltration branch of thebalancing system, according to embodiments of the disclosed subjectmatter.

FIG. 4B shows a volumetric balancing system of an extracorporeal bloodtreatment system with a secondary flow that is selectively connectablein a push pull relationship with an ultrafiltration branch of thebalancing system, where flow through the secondary line is connected inpush pull relationship to the flow in the ultrafiltration branch inorder to compare the pumping rates, according to embodiments of thedisclosed subject matter.

FIG. 5A shows a further pumping system which may be used for balancingmultiple fluids under control of a controller and which is automaticallyselectively configurable to permit calibration of pumps respective toeach fluid to permit higher accuracy of fluid balancing, according toembodiments of the disclosed subject matter.

FIG. 5B shows an embodiment of a flow sensor that may be used in placeof any of the flow sensors of the embodiments disclosed herein.

FIG. 5C shows the pumping system of FIG. 5A in a configuration forcalibrating a flow rate, according to embodiments of the disclosedsubject matter.

FIG. 6 illustrates control embodiments for performing a calibration formultiple flow rates for various balancing system embodiments of thedisclosed subject matter.

FIG. 7 illustrates control embodiments for checking and/or adjustingflow balance prediction models for various balancing system embodimentsof the disclosed subject matter.

FIG. 8 shows how all the embodiments may be modified such that bloodside flow is regulated in order to control transmembrane pressure tocreate variants of the disclosed subject matter.

FIG. 9 illustrates an active accumulator that may be used with any ofthe embodiments in place of a passive accumulator to create newembodiments, according to embodiments of the disclosed subject matter.

FIG. 10 shows a method for calibrating one pump against another in whicha volumetric efficiency of one of the pumps is altered so as to speedthe matching of flow rates in a push-pull arrangement, according toembodiments of the disclosed subject matter.

FIG. 11 shows a method for calibrating one pump against another in whicha calibration is set up by controlling total flow so as to avoidconditions that are predicted to result in a slow speed of matching offlow rates in a push-pull arrangement, according to embodiments of thedisclosed subject matter.

FIGS. 12A and 12B show multiple line peristaltic pump configurations inwhich the flow in two lines are adjusted relative to each other byrestricting flow into or out of the pumps by a control valve such thatthe flow can be matched, according to embodiments of the disclosedsubject matter.

FIG. 13 shows properties of a peristaltic pump with a variable rotationrate, according to embodiments of the disclosed subject matter.

FIGS. 14 and 15 illustrate methods and systems for matching flowsbetween pumps for purposes of calibration using a common flow pathaccording to embodiments of the disclosed subject matter.

FIGS. 16 through 19 illustrate systems for conserving treatment fluidused for calibration according to embodiments of the disclosed subjectmatter.

FIG. 20 shows a generalized schematic diagram of a system for balancingflows according to embodiments of the disclosed subject matter.

FIG. 21 shows a graph that illustrates correcting for error in flowbalancing in systems such that shown in FIG. 20 and elsewhere hereinaccording to embodiments of the disclosed subject matter.

DETAILED DESCRIPTION

FIG. 1A shows a generic control valve that can flow fluid into aselected fluid line. In the succeeding embodiments, the control valve102 allows a flow from an inlet line 103 to be selectively transferredto either line 104 or 105 under control of a controller. At any point inthe present disclosure such a control valve is symbolized as shown at102 and may be embodied by any suitable multipath control valveincluding valves that employ pinching of flexible flow channels,rotating sealed selectors, etc. An advantageous type of control valve102 is shown in FIG. 1B at 101. FIG. 1B shows a type of control valvethat is beneficial in disposable circuits in which permanent clampingmembers open and control tubing branches by pinching, such that thetubing branches can be hermetically sealed and permanently connected byan inexpensive branch. Three lines 103, 104, and 105 are joined by ajunction 111. Flow through lines 104 and 105 are permitted or restrictedusing control clamps 108 and 110. A controller can cause control clamp108, for example a solenoid-retracted, spring driven pinching device, tobe closed while opening control clamp 110 (of the same structure ascontrol clamp 108) thereby selecting flow from line 103 through line105. The controller can cause control clamp 108 to be open while closingcontrol clamp 110 thereby selecting flow from line 103 through line 104.The lines 103, 104, and 105 may be flexible tubing. The junction 111 maybe a Y-junction, T-junction, or any suitable member.

FIG. 1C illustrates a controller 50 that may be present in all theembodiments described herein and assumed to be present in alldescriptions of a controller, the figure showing elements connected to,or subsumed within one or more controllers that perform the one or morecontrol or computational functions described in connection with theembodiments. The controller 50 may have sensors 51, 52 such as pressureand/or temperature and/or flow rate and/or weight sensors. Thecontroller may have data storage including non-volatile storage 56and/or random access memory 58, flash or other data storage. A display60, loudspeaker 62 and/or other user interface outputs may be connectedor subsumed by the one or more controller represented by controller 50.User input devices such as a keyboard and mouse 62, touchscreen, gestureinput, nerve-signal input, or other input device may be connected orsubsumed.

FIG. 2A is a schematic diagram of an extracorporeal blood treatmentsystem 119, for example, a dialysis system in which an additionalinfusion stream is provided and balanced against an effluent stream. Ablood circuit 160 has arterial line 160A and venous line 160B thattransfer blood from a patient access 150 to a treatment device 120, herea dialyzer 120, and back to the patient access 150. The patient access150 is illustrated by a fistula, which may be accessed by a dual lumenneedle or by a pair of needles (not shown). Other types of accesses maybe used to provide for a continuous flow of blood. Blood is pumpedthrough the blood circuit 160 by a pump 142, for example a peristalticpump 142. Fluid from a source of a first medicament 124, for example,dialysate 124 is pumped by a pump 132 into a dialysate compartment ofthe dialyzer 120 and spent dialysate is transferred out of the dialysatecompartment of the dialyzer 120 by a pump 140 through line 156. Thepumps 132 and 140 are controlled in such a fashion that a net fluidbalance is maintained with a net positive or net negativeultrafiltration from the patient. This may be achieved by controllingthe rate ratios of the pumps 132 and 140. An additional fluid may besupplied to the blood circuit 160 by pumping fluid from a fluid source122 using a pump 130. The additional fluid from source 122 may besaline, blood-normal replacement fluid, citrate, or a medicament ordrug. The additional mass or volume of fluid from the source 122 at therate determined by the rate of pump 130 may be controlled such that thecombined flow through pumps 130 and 132 is controlled against the rateof pump 140 such that the target net ultrafiltration rate is achieved.The rate of the pumps may be provided using an encoder on each pumpwhich informs a controller 166 of the exact number of rotations per unittime of the pump (assuming the pumps are peristaltic pumps, but acorresponding method may be used for other types of pumps). Note thatother pumping rate sensors are also possible, for example where steppermotor drives are used with the peristaltic pumps, the drive pulses maybe counted to determine the speed of the pumps rather than an encoder.In the present embodiment, controller 166 may control the rates of allthe pumps or a subset sufficient to provide the balance described.

Embodiments of the extracorporeal blood treatment system 119 may presentthe problem that the precision with which the rates of flow through thepumps 130, 132, and 140 can be controlled and/or measured isinsufficient for the desired precision of fluid balance of the patientover the length of a predefined treatment. To allow for the regulationof the flow rates contributing to the balancing described, controlvalves 136, 134, 146 and pressure sensors 125, 126, 127, 128, 139, 141,and 145 may be provided. The pressure sensors 125, 126, 127, 128, 139,141, and 145 may be of any suitable type including pressure pod typesensors that employ a strain gauge pressure sensor to produce anelectrical signal that can be applied to the controller 166. Thepressure sensors 125, 126, 127, 128, 139, 141, and 145 may also be ofthe type with an air trap chamber with an air line that leads to apressure transducer. These sensors and control valves are connected tothe controller 166 which receives the pressure signals from the pressuresensors and controls the flow of fluid through the control valves. Usingthe control valve 136, flow from the fluid line 162 can be selectivelydiverted by the controller 166 to the branch line 155 so that fluid fromline 162 flows through the junction 147 into the branch line 154. Usingthe control valve 134, flow from the fluid line 162 can be selectivelydiverted by the controller 166 to the branch line 154 so that fluid fromline section 149 flow through the junction 134 into the branch line 154.In a first position, the control valves 136 and 134 may divert flow froma selected one, or both, of the sources 124 and 122 through the branchline 154 through the control valve 146 and into the effluent line 156. Acompliant flow accumulator 138 reduces the strength of pressure pulsesto allow for a smoothly varying pressure signal from the pressure sensor139. The accumulator may be a clear-walled rigid chamber with an airreservoir whose volume can be established by manually injecting airthrough a septum with a hypodermic needle to position a meniscus at agraduation marked on the chamber. The accumulator may also be a bladderwith an urging mechanism such as spring which is positioned to resistthe expansion of the bladder.

FIG. 2B is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from a firstsource is diverted directly through a branch line to the effluent outputto permit the calibration, or confirmation of calibration of a pumpingrate for the fluid from the first source, to be obtained. In thisconfiguration, the controller 166 causes the flow control valves 134 and146 to divert flow from the source 124 to the branch line 154 andfinally to the effluent line 156. The flow path so-defined uses twopumps with a closed circuit such that any difference in the flow ratesof the pump 132 and the pump 140 will manifest a pressure change by thepressure sensor 139. The controller may perform a flow test in thisconfiguration for a test interval to measure the degree to which thepump rates differ by calculating the rate of change of pressureindicated by the pressure sensor 139. In this mode, the controller 166may step through a range of flow rates while sampling and storingpressure signals from pressure sensors 126, 128, 141, and 145, adjustingthe speed of one of the pumps to reduce or eliminate the change inpressure of pressure sensor 139 (thereby matching the pumping rates),and storing the pressure differentials across each pump 132 and 140 thatcorresponding to the matched flow rates. This process may be performedbefore the beginning of each treatment after a fluid circuit has beenchanged, after a component has been changed such as a tubing segment, orafter any other change in the system that could affect the flowperformance.

In the previous, or other, embodiments, the configuration of FIG. 2B canbe established briefly during a treatment merely to confirm a match, ora difference, between the pumping rates of the pumps 132 and 140. Thesystem configuration of FIG. 2A can be modified by eliminating the fluidcircuit for fluid from source 122 whereby the only balanced flow thatneeds to be maintained is from a single source 124. In such a system,the degree to which the flow rates of two independently-controlled pumpsmatch can be tested momentarily, for example over a period of 2 seconds,by switching the control valves 134 and 146 to divert the flow andsampling the pressure signal from pressure sensor 139. In embodiments,the duration of the diversion may be long enough to establish a reliableindication to verify that the pumping rates are equal. The controller166 may be further programmed to perform a correction of the rate of oneof the pumps in order to more closely match the pumping rates of the twopumps. In an embodiment, the rate of rise or fall of the pressureindicated by the pressure sensor 139 is correlated with a correctionbased on a lookup table, stored in a memory accessible by the controller166. The lookup table may correlate the rate of rise or fall and theabsolute speed of one of the pumps and provide, for each pair, acorrection of the speed of one of the pumps 132 and 140. In additionalembodiments, a lookup table may store a function that correlates thepressure rise across a pump and an absolute speed that pump with atarget pressure rise across the other pump that produces the same flowrate. The function is then corrected using the signal from pressuresensor 139 such that the pressure rises across the pumps, which can bemeasured continuously, can be used during treatment operation, tomaintain a balanced flow. In another embodiment, the controller 166 mayprogressively change the rate or rates of pumping according to anegative feedback control algorithm to control the speed of one of thepumps 132 and 140 to reduce the pressure change indicated by thepressure sensor 139.

FIG. 2C is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from a secondsource is diverted directly through a branch line to the effluent outputto permit the calibration, or confirmation of calibration of a pumpingrate of fluid from the second source, to be obtained. In thisconfiguration, the controller 166 causes the flow control valves 136 and146 to divert flow from the source 122 to the branch line 154 andfinally to the effluent line 156. The flow path, so-defined, uses twopumps 130 and 140 in a closed circuit such that any difference in theflow rates of the pump 130 and the pump 140 will manifest a pressurechange by the pressure sensor 139. The controller may perform a flowtest in this configuration for a test interval to measure the degree towhich the pump rates differ by calculating the rate of change ofpressure indicated by the pressure sensor 139. In this mode, thecontroller 166 may step through a range of flow rates while sampling andstoring pressure signals from pressure sensors 125, 127, 141, and 145,adjusting the speed of one of the pumps 130 and 140 to reduce oreliminate the change in pressure of pressure sensor 139 (therebymatching the pumping rates), and storing the pressure differentialsacross each pump 130 and 140 that correspond to the matched flow rates.This process may be performed before the beginning of each treatmentafter a fluid circuit has been changed, after a component has beenchanged such as a tubing segment, or after any other change in thesystem that could affect the flow performance.

In the previous, or other, embodiments, the configuration of FIG. 2C canbe established briefly during a treatment merely to confirm that thematch, or the difference, between the pumping rates of the pumps 132 and140. The system configuration of FIG. 2A can be modified by eliminatingthe fluid circuit for fluid from source 122 whereby the only balancedflow that needs to be maintained is from a single source 124. In such asystem, the degree to which the flow rates of twoindependently-controlled pumps match can be tested momentarily, forexample over a period of 2 seconds, by switching the control valves 136,and 146 to divert the flow and sampling the pressure signal frompressure sensor 139. In embodiments, the duration of the diversion maybe long enough to establish a reliable indication to verify that thepumping rates are equal. The controller 166 may be further programmed toperform a correction of the rate of one of the pumps in order to moreclosely match the pumping rates of the two pumps 130 and 140. In anembodiment, the rate of rise or fall of the pressure indicated by thepressure sensor 139 is correlated with a correction based on a lookuptable, stored in a memory accessible by the controller 166. The lookuptable may correlate the rate of rise or fall and the absolute speed ofone of the pumps and provide, for each pair, a correction of the speedof one of the pumps 130 and 140. In additional embodiments, a lookuptable may store a function that correlates the pressure rise across apump and an absolute speed that pump with a target pressure rise acrossthe other pump that produces the same flow rate. The function is thencorrected using the signal from pressure sensor 139 such that thepressure rises across the pumps, which can be measured continuously, canbe used during treatment operation, to maintain a balanced flow. Inanother embodiment, the controller 166 may progressively change the rateor rates of pumping according to a negative feedback control algorithmto control the speed of one of the pumps 132 and 140 to reduce thepressure change indicated by the pressure sensor 139.

FIG. 2D is a schematic diagram of an extracorporeal blood treatmentsystem as in FIG. 2A in a configuration in which flow from the first andsecond sources are diverted directly through branch lines to theeffluent output to permit the calibration, or confirmation ofcalibration of a pumping rate for the combined fluids flow from thefirst and second sources, to be obtained. In this configuration, thecontroller 166 causes the flow control valves 134, 136, and 146 todivert flow from both the source 122 and the source 124 to the branchline 154 and finally to the effluent line 156. The flow path,so-defined, uses the two pumps 130 and 132 to push the flow and one pump140 to pull the flow through the branch line 154 in a closed circuitsuch that any difference in the pushed and pulled flow rates will acause a pressure change in the accumulator 138 indicated the pressuresensor 139. The controller may perform a flow test in this configurationfor a test interval to measure the degree to which the pump rates differby calculating the rate of change of pressure indicated by the pressuresensor 139. In this mode, the controller 166 may step through a range offlow rates while sampling and storing pressure signals from pressuresensors 125, 127, 126, 128, 141, and 145, adjusting the speed of one ortwo of the pumps 130 and 140 to reduce or eliminate the change inpressure of pressure sensor 139 (thereby matching the pumping rates),and storing the pressure differentials across each of the pumps 130,132, and 140 that correspond to the matched flow rates. This process maybe performed before the beginning of each treatment after a fluidcircuit has been changed, after a component has been changed such as atubing segment, or after any other change in the system that couldaffect the flow performance.

In the previous, or other, embodiments, the configuration of FIG. 2D canbe established briefly during a treatment merely to confirm that thematch, or the difference, between the combined pumping rates of thepumps 130 and 132 and the individual pump 140. The degree to which theflow rates of the independently-controlled pumps match can be testedmomentarily, for example over a period of 2 seconds, by switching thecontrol valves 134, 136, and 146 to divert the flow and sampling thepressure signal from pressure sensor 139. In embodiments, the durationof the diversion may be long enough to establish a reliable indicationto verify that the combined pumping rate of pumps 130 and 132 is equalto that of pump 140. The controller 166 may be further programmed toperform a correction of the rate of one or two of the pumps in order tomore closely match the push and pull pumping rates. In an embodiment,the rate of rise or fall of the pressure indicated by the pressuresensor 139 is correlated with a correction based on a lookup table,stored in a memory accessible by the controller 166. The lookup tablemay correlate the rate of rise or fall and the absolute speed of one ofthe pumps and provide, for each pair, a correction of the speed of oneor two of the pumps 130, 132, and 140. In this and any of the foregoingembodiments, the speed of both push and pull pumps may be adjustedrather than a single one of the push and pull pumps. In additionalembodiments, a lookup table may store a function that correlates thepressure rise across a pump and an absolute speed that pump with atarget pressure rise across the other pump that produces the same flowrate. The function may then be corrected using the signal from pressuresensor 139 such that the pressure rises across the pumps, which can bemeasured continuously, can be used during treatment operation, tomaintain a balanced flow. In another embodiment, the controller 166 mayprogressively change the rate or rates of pumping according to anegative feedback control algorithm to control the speed of one, two, orthree of the pumps 130, 132 and 140 to reduce the pressure changeindicated by the pressure sensor 139.

As explained, it is possible to control the fluid balance in theextracorporeal circuit by simply matching the cumulative pump rates ofmultiple inflows with the pump rate of the effluent outflow. Inpractice, it may be difficult to maintain pump rates with sufficientaccuracy to achieve clinically effective fluid balance. As describedabove, switching in a push-pull arrangement of pumps whose flows are tobe balanced, allows a pressure signal to indicate to a controllerwhether the pumping rates are equal and also, by sampling the pressuresignal, the rate of change of the pressure of an accumulator canindicate the magnitude of the imbalance of pumping rates. Thus thechange of pressure per unit time can be correlated to a magnitude ofpumping speed difference based on the properties of the accumulator andthe fluid circuit. This relationship may be experimentally determinedand stored in a lookup table or a formula and used by the controller toadjust the speed of one or more of the push and pull pumps.

Although in the foregoing embodiments, pumps, pressure sensors, and flowcontrol valves were described as separate elements, it is possible forcomposite devices to be employed which provide the same functionality inintegrated devices in order to reduce the parts count. Further pumps ofvarying types may be used, including piston pumps, turbine pumps, andother types of pumps. Permanent and disposable circuits may also beemployed to form the fluid circuits described above and below. Inadditional embodiments, instead of diverting flow to a branch of tubingand measuring a change in pressure due to differing flow rates ofpushing and pulling pumps, it is possible to temporarily divert the flowto a gravimetric sensor which can measure a mass of fluid in a fixedperiod of time to provide a calibration against the pressure sensorwhich may then be used by the controller 166 to regulate the flow offluid. Such a gravimetric device may use a self-emptying chamberattached to a self-zeroing scale.

FIG. 3A is a schematic diagram of an extracorporeal blood treatmentsystem 319, for example, a dialysis system in which two additionalinfusion streams are provided and balanced against an effluent stream. Ablood circuit 360 has arterial line 360A and venous line 360B thattransfer blood from a patient access 350 to a treatment device 320, herea dialyzer 320, and back to the patient access 350. The patient access350 is illustrated by a fistula, which may be accessed by a dual lumenneedle or by a pair of needles (not shown). Other types of accesses maybe used to provide for a continuous flow of blood. Blood is pumpedthrough the blood circuit 160 by a pump 342, for example a peristalticpump 342. Fluid from a source of a first medicament 324, for example,dialysate 324 is pumped by a pump 332 into a dialysate compartment ofthe dialyzer 320 and spent dialysate is transferred out of the dialysatecompartment of the dialyzer 320 by a pump 373 through line 356. Thepumps 330, 332, 334, and 373 are controlled in such a fashion that a netfluid balance (of the patient including a target net ultrafiltration) ismaintained. This may be achieved by controlling the rate ratios of thepumps 330, 332, 334, and 373. Note that pumps 330, 332, and 334 provideflow fluid into the system and their combined flow is balanced againstthe flow through the effluent pump 373. Here, fluids are exemplified bydialysate from a source 324 and two replacement fluids or medicamentsRF1 and RF2, from respective sources 322 and 321. Here and elsewhere,the sources may be any source of fluid and may provide any type offluid, although here they are illustrated using containers as examples.In the present or any of the embodiments, examples of types ofmedicaments include citrate, pre-diluent, replacement fluid,blood-normal replacement fluid or saline, any medicament or a drug.

The rate of the pumps may be indicated to the controller 366 by signalsfrom an encoder in each pump 330, 332, 334, and 373 which informs acontroller 166 of the exact number of rotations per unit time of thepump (assuming the pumps are peristaltic pumps, but a correspondingmethod may be used for other types of pumps). Note that other pumpingrate sensors are also possible, for example where stepper motor drivesare used with the peristaltic pumps, the drive pulses may be counted todetermine the speed of the pumps rather than an encoder. In the presentembodiment, controller 366 may control the rates of all the pumps or asubset sufficient to provide the balance described. For example, one ofthe pumps may run at a predefined rate that is not actively adjusted bythe controller 366, for example, the effluent pump, and the others maybe adjusted by the controller 366. In embodiments, all the pumps 330,332, 334, and 373 are regulated by the controller.

As in the foregoing embodiments, embodiments of the extracorporeal bloodtreatment system 319 may present the problem that the precision withwhich the rates of flow through the pumps 330, 332, 334, and 373 can becontrolled and/or measured is insufficient for the desired precision offluid balance of the patient over the length of a predefined treatment.To allow for the regulation of the flow rates contributing to thebalancing described, flow sensors 340, 344, 346, and 347 are provided.In embodiments, the flow sensor for each pump is used by the controller366 to regulate the balance based on a stored ultrafiltration rate ortotal ultrafiltrate volume (mass) to be removed in a treatment. The netfluid withdrawal or infusion can be controlled by suitable regulation ofthe flow rate and numerical accumulation of volume or mass ultrafilteredfrom (infused into; i.e., negative ultrafiltered from) the patient. Therate or total amount of each medicament from sources 321, 322, and 324can be regulated accordingly. During normal operation the flowconfiguration of FIG. 3A may be used whereby the fluids from the threesources 321, 322, and 324 are pumped, by pumps 330, 332, 334, into theblood line 360A and the treatment device 320, respectively and effluentfluid is drawn from the treatment device 320 by pump 373. In variationsof the system a greater or smaller number of fluids are used.

To calibrate or confirm the calibration of flow sensor 340, the controlvalve 362 may be set to establish a flow of fluid from source 322directly into the effluent line 356 where the flow is additionalmeasured by flow sensor 347. Since flow sensor 347 is in an effluentline, it may be based on a permanent flow measurement system with highaccuracy that need not provide for a sterile flow path. For example, ahigh accuracy flow meter of a positive displacement type with pistonsand a crank connected to an encoder may be used. High precisiontransit-time flow meters may also be used, which may label the effluentfluid using a thermal label without concern about rendering itphysiologically incompatible or denatured in any way. Other examples ininclude turbine meters, vortex shedding flow meters, and dynamicgravimetric mass flow meters. In the embodiment 319, control valves 362,364, and 366 permit the flow from each source 321, 322, and 324 to beindividually or collectively conveyed directly to the drain line 356 andthereby through the flow sensor 347. In embodiments, the flow sensor 347is of a higher accuracy than the flow sensors 340, 344, and 346. Byflowing from each source 321, 322, and 324 individually or collectivelythrough a respective one of the flow sensors 340, 344, and 346 andconveying the fluid directly to the drain line 356 and thereby throughthe flow sensor 347, the flow sensors 340, 344, and 346 may beindividually or collectively verified or calibrated based upon a moreaccurate flow given by flow sensor 347. In embodiments, the flow sensor347 is based on a standard traceable measurement mechanism, such asNational Institute of Standards and Technology. In embodiments, the flowsensor 347 provides a direct measurement of volume or mass and the flowsensors 340, 344, and 346 indicate flow by measuring a quantity that isindirectly connected with volume or mass such as pressure loss in a flowrestriction, a parameter associated with flow velocity such as time offlight of a fluid label, a turbine speed, etc.

In embodiments, at the start of a treatment, fluid from each source 321,322, and 324 is individually conveyed through a respective one of theflow sensors 340, 344, and 346 and further conveyed through the drainline 356 and thereby through the flow sensor 347. The controller 366configures the control valves 362,364, and 366 so as to establish eachflow so that each of the flow sensors 340, 344, and 346 is individually,in turn, connected by a fixed flow path with the flow sensor 347. Anexample configuration is shown in FIG. 3B where the fluid from source322 (RF1) is diverted to the drain line 356 and only the pump 330 isoperated so that there is a direct flow path through the flow sensor340, to be calibrated or checked, and the true flow sensor 347 and outto a drain 344. The other flow sensors 332 and 334 would havecorresponding configurations and pump operations. Note that the effluentpump 373 is not operated during these individual calibrations. For eachconfiguration, a range of flow rates may be established and a correctionfactor recorded by the controller, based on the difference between thetrue flow rate given by flow sensor 347 and the flow rate indicated bythe respective one of the flow sensors 340, 344, and 346. The set ofcorrections provides calibration data to allow a more correct flow rateindication by each of the flow sensors 340, 344, and 346 during atreatment. In further embodiments, each of the flow sensors 340, 344,and 346 is connected in turn during treatment for a brief time toconfirm the accuracy of its respective flow rate indication to thecontroller 366. During each such test, a calibration adjustment may bestored by the controller 366 and used to correct the later flow rateindication of the tested one of the flow sensors 340, 344, and 346.Further, the controller may back-correct the net fluid volume transfersto or from the patient based on the error indicated by such tests. Inresponse to the magnitude of the error, the controller 366 may modifythe net fluid transfer to or from the patient by adjusting the commandedultrafiltration rate or the rate of flow of replacement fluid to thepatient. The controller 366 may also command the injection of a bolus ofreplacement fluid after or during the treatment. The controller 366 mayoutput an indication on a user interface of a recommended net change inultrafiltration or bolus injection to permit an operator to override.The output may show the magnitude of the error and the correction. Theerror may be stored in a treatment log or machine performance log orboth. In an example, a total cumulative volume reverse ultrafiltered tothe patient (i.e. infused) may be reduced by an interpolated calibrationfactor retroactively applied between two calibration intervals during atreatment. The controller 366 may store the historical flow data andapply the corrected calibration factor to the historical data to arrivethereby at a correct cumulative reverse ultrafiltered volume (i.e.,volume infused) to the patient. The pump rates may then be adjusted bythe controller responsively to a remaining treatment time to arrive at atarget net ultrafiltration volume.

FIG. 4A shows a volumetric balancing system of an extracorporeal bloodtreatment system with a secondary flow that is selectively connectablein a push pull relationship with an ultrafiltration branch of thebalancing system, according to embodiments of the disclosed subjectmatter. In extracorporeal blood treatment system 419, for example, adialysis system balances a dialysis stream and an additional infusionstream. A blood circuit 460 has arterial line 460A and venous line 460Bthat transfer blood from a patient access 470 to a treatment device 402,here a dialyzer 402, and back to the patient access 470. The patientaccess 470 is illustrated by a fistula, which may be accessed by a duallumen needle or by a pair of needles (not shown). Other types ofaccesses may be used to provide for a continuous flow of blood. Fluidfrom a source 424 of a first medicament, for example, dialysate ispumped by a volumetric balancing mechanism 471 into a dialysatecompartment of the dialyzer 402 and spent dialysate is transferred outof the dialysate compartment of the dialyzer 402 through line 432. Aninfusion stream flows medicament or drug or any other fluid from asource 422 to the venous line 460B via pump 434. Although one infusionstream from source 422 is illustrated, any number of infusion streamsmay be added to form variations of the present embodiment. Thevolumetric balancing mechanism 471, which may be, for example, any typethat volumetrically balances (provides equal flow volumes) of the flowsin ingoing 481 and outgoing 482 streams, balances the flow of dialysatefrom source 424 flowing in line 430 against the flow of spent dialysatein line 432. During a treatment, blood is pumped through the bloodcircuit 460 by a pump 465, for example a peristaltic pump 465. Duringtreatment, fluid flows from source 422 into a venous blood line 460B,from source 422, through a control valve 432, pumped by pump 434.Although the flow of fluid from source 422 is shown being added to thevenous blood line 460B, in other embodiments, the fluid is conveyed tothe arterial blood line 460A using suitable connections. A netultrafiltrate volume is controlled by an additional effluent stream thatis pumped by pump 436 through ultrafiltrate bypass line 408, which joinsthe balanced spent dialysate flow in line 432 and exits the drain 410. Acontroller 466 controls the pump 434 and may control the pump 436. Tobalance the flow of fluid from source 422, the ultrafiltrate bypass flowmay be increased to include both a target ultrafiltrate and a new flowof fluid from the source 422. Thus, the volume flowing through line 408during treatment would be the total of the flow from the source 422through line 435 plus the rate corresponding to the targetultrafiltrate.

FIG. 4B shows a volumetric balancing system of an extracorporeal bloodtreatment system with a secondary flow that is selectively connectablein a push pull relationship with an ultrafiltration branch of thebalancing system, where flow through the secondary line is connected inpush pull relationship to the flow in the ultrafiltration branch inorder to compare the pumping rates, according to embodiments of thedisclosed subject matter. At a time of calibration (illustrated in FIG.4B), the rate of pumping of pump 436 and of pump 434 can be controlledby controller 466 to be equal while the pumps are placed, temporarily,in a push-pull relationship by diverting all flow in line 435 to thebranch line 441 and into line 408 such that a pressure change in anaccumulator 412 will be indicated by a pressure sensor 415 connected tothe accumulator whose signal is applied to the controller 466. Thecontrol parameters used to determine the flows in pumps 434 and 436 maybe adjusted to compensate the fluid balance error for multiple differentflow rates thereby permitting a balance calibration. Note thiscalibration does not permit an error in absolute flow rates to becompensated but rather merely an error in the flow balance between thecommanded rate of pump 436 and that of pump 434. The push-pull flow isestablished by controlling control valves 432 and 430. The calibrationprocedure can be performed during a treatment or prior to eachtreatment. The calibration process may be preceded by a verificationprocedure which indicates whether the commanded flows are balanced (by apressure change in the accumulator 412 indicated by pressure sensor415). If the verification procedure indicates that the flows arebalanced, the calibration may be skipped. The verification procedure maybe performed for a smaller number of flow rates than a calibrationprocedure.

Here, fluids are exemplified by dialysate from a source 424 and areplacement fluid or medicaments RF from source 422. Here and elsewhere,the sources may be any source of fluid and may provide any type offluid, although here they are illustrated using containers as examples.In the present or any of the embodiments, examples of types ofmedicaments are citrate, prediluent, replacement fluid, blood-normalreplacement fluid or saline, any medicament or a drug. The rate of thepumps may be indicated to the controller 466 by signals from an encoderin each pump which informs the controller 466 of the exact number ofrotations per unit time of the pump (assuming the pumps are peristalticpumps, but a corresponding method may be used for other types of pumps).Note that other pumping rate sensors are also possible, for examplewhere stepper motor drives are used with the peristaltic pumps, thedrive pulses may be counted to determine the speed of the pumps ratherthan an encoder. The accumulator 412 and pressure sensor 415 may be asdiscussed with reference to the corresponding element of earlierembodiments. The volumetric balancing mechanism 471 may be as describedin U.S. Pat. No. 7,112,273 to Weigel et al. The volumetric balancingmechanism 471 may be replaced by any type of flow balancing systemincluding ones that use scales to weigh the cumulative total of freshand spent fluids.

FIG. 5A shows a further pumping system which may be used for balancingmultiple fluids under control of a controller and which is automaticallyselectively configurable to permit calibration of pumps respective toeach fluid to permit higher accuracy of fluid balancing, according toembodiments of the disclosed subject matter. Independent pumps 512, 514,516, and 520 flow fluids from source 524 (which may be dialysate orother medicament, for example), fluid from source 522, which may be amedicament, and effluent fluid from a blood treatment device 502 (e.g.,a dialyzer) at rates dependent command signals from a controller 566. Inan embodiment, dialysate circulates from source 524 though the pump 512through line 528 and line 562 into a dialysate compartment of a dialyzer502. Spent dialysate flows from the dialysate compartment of thedialyzer 502 through lines 530 and 531 pump 516 and to a drain 510through line 532. Blood is circulated through the blood compartment ofthe dialyzer 502 by a blood circuit 560 which has an arterial line 560Aand a venous line 560B. Replacement fluid flows from source 522 throughline 553, pump 514, and lines 549, and 551 into the arterial line 560A.The pumps 512, 514, and 516 are controlled in a manner that allows thecombination of ingoing fluids (fluids from sources 522, 524 flowing atrates of pumps 512 and 514) to be balanced against the flow of effluentpumped by pump 516. Any of the fluids can be selectively pumped througha flow sensor 509 using control valves 515, 517, and 518. FIG. 5B showsan embodiment of a flow sensor that may be included in flow sensor 509.A fluid flows through a line 507 through a flow restriction 505. Thefluid pressure on either side of the restriction indicates the flowrate. Pressure sensors 503 indicate the pressure on either side and areconnected to the controller 566 which may convert the pressure signalsto a flow rate by means of a calibration data table or formula stored inthe controller 566. Other types of flow sensors 509 can also be used.The flow restriction 505 may be a length of tubing of a precise innerdiameter of non-compliant material and with a coefficient of thermalexpansion. Instead of a low coefficient of thermal expansion, the lengthof tubing may be temperature controlled during calibration or bycompensating for size changes due to temperature numerically during thecalibration procedure.

At a time of calibration (illustrated in FIG. 5C), the rate of pumpingof each of the pumps 512, 514, and 516 can be measured using the flowsensor 509 by diverting a respective one of the flows through the flowsensor 509. The control valves may be configured automatically by thecontroller before treatment or during a treatment and pumping rates maybe varied according to a calibration protocol. The stored calibrationdata may show a flow rate corresponding to each pump rate, the pump ratebeing the final measured or commanded rate, for example, the rotationalvelocity of the shaft of a peristaltic actuator, the drive pulses of astepping motor, or the pulses from an encoder. Data from the flow sensor509 indicating the flow rate may be use calibrate each of the pumps 512,514, and 516. FIG. 5C illustrates the configuration in which the flow isdiverted through the flow sensor 509 by the control valve 515. It can beconfirmed by inspection that the lines 540, 542, 547, 556, and controlvalves 517 and 518 are arranged to permit other fluids, includingeffluent, to flow through the flow sensor 509. Here, fluids areexemplified by dialysate from a source 524 and a replacement fluid ormedicament RF from a source 522. Here and elsewhere, the sources may beany source of fluid and may provide any type of fluid, although herethey are illustrated using containers as examples. In the present or anyof the embodiments, examples of types of medicaments are citrate,pre-diluent, replacement fluid, blood-normal replacement fluid orsaline, any medicament or a drug. The rate of the pumps may be indicatedto the controller 566 by signals from an encoder in each pump whichinforms the controller 466 of the exact number of rotations per unittime of the pump (assuming the pumps are peristaltic pumps, but acorresponding method may be used for other types of pumps). Note thatother pumping rate sensors are also possible, for example where steppermotor drives are used with the peristaltic pumps, the drive pulses maybe counted to determine the speed of the pumps rather than an encoder.

FIG. 6 illustrates control embodiments for performing a calibration formultiple flow rates applicable to any of the various extracorporealblood treatment or balancing system embodiments of the disclosed subjectmatter. According to the embodiments of FIG. 6, a controller controlsthe pumping rate of one or more pumps as well one or more control valvesto establish configurations of flow balancing systems or devices, forexample those of the foregoing or later figures. A digital controllermay be programmed to perform the operations presently described, duringa set-up phase after a new treatment configuration is established, forexample by installing a new disposable and during a priming operation orduring an initial phase of treatment. Alternatively, the operation maybe performed in a production facility and the calibration parametersneeded for the flow model described with reference to S114 may beenclosed with a disposable tubing set.

In an initial operation S102, a push-pull configuration is establishedbetween pumps whose flows are to be balanced or proportioned asdescribed herein. This configuration may be established by suitableoperation of one or more valves as described herein and in otherembodiments capable of establishing a closed circuit between the twopumps, a flow imbalance between which may be detected. The controllermay store multiple preselected values of pump speed or a series ofvalues may be computed according to a formula such that, at S104, avalue of pump speed may be selected. Then at S106, the pump speed forthe push pump may be set at the selected value and at S108, a pump speedfor the pull pump may be estimated to match the push pump responsivelyto a flow model stored in a memory or other data storage in thecontroller. Then at S110, the estimated value of the pull pump speed maybe dynamically changed based on a proportional-differential controlalgorithm or some other algorithm until, using the accumulator pressuresensor, a match of the push and pull flows, within a predefined range,is established. The match may be determined by seeking a control goal ofzero rate of change of accumulator pressure. At S114, one or morepressures (e.g., one or more of the pump inlet and outlet pressures asdescribed in the above-described figures) and the pull pump speed forthe currently selected push pump speed are recorded by the controller.Next, at S116, the controller determines if further pump speeds of Npump speeds (N being a predefined number of pump speeds selected tocover a range of flow rates suitable for generating a sufficientlyaccurate flow model of the pull pump speeds corresponding to anypredefined push pump speeds) remain to be selected to complete acalibration operation. If further push pump speeds are to beimplemented, then a next push pump speed in a predefined schedule of Npump speeds is selected (S112) and the push pump speed is established bythe controller at S106. If the N^(th) push pump speed has already beenestablished at S116, then the controller takes the calibration data (allthe pressures and pump speeds recorded at S114) and generates a model byfitting the data at S118. Alternatively, the calibration data may bestored and used directly or by interpolating or extrapolating toidentify the pull pump speed that best corresponds to a balanced flowgiven a given push pump speed.

In the foregoing it was assumed the push pump speed was established andthe pull pump speed was determined to match the push pump speed, but itshould be clear that in alternative embodiments, the pull pump speed maybe first selected and a matching push pump speed determined in S110.Note also that the calibration procedure may be applied to multiple pushpumps in push-pull relation to one or more pull pumps. This increasesthe dimensionality of the model Q=f(P_(i,j), ω_(pull,i)) and thecombination of pumping speeds to be established but otherwise followsthe same operations described above. The model may be formed andcalibrated to provide a flow rate that is proportional (approximatelyequal) to the flow rate of the tandem pump.

Note that in the present embodiment, it is assumed that pump speed maybe controlled by selecting a shaft speed of a peristaltic pump but othertypes of pumps may be employed and speed selected by an appropriatecontrol mechanism.

FIG. 7 illustrates control embodiments for checking and/or adjustingflow balance prediction models for various extracorporeal bloodtreatment or balancing system embodiments of the disclosed subjectmatter. According to the embodiments of FIG. 7, a controller controlsthe pumping rate of one or more pumps as well one or more control valvesto establish configurations of flow balancing systems or devices, forexample those of the foregoing or later figures. A digital controllermay be programmed to perform the operations presently described, duringa set-up phase after a new treatment configuration is established, forexample by installing a new disposable and during a priming operation orduring an initial phase of treatment. Alternatively, the operation maybe performed in a production facility and the calibration parametersneeded for the flow model described with reference to S220 may beenclosed with a disposable tubing set. The method of FIG. 7 differs fromthat of FIG. 6 in that the one or more pumps are calibrated to generatea model that is responsive to both inlet pressure or inlet and outletpressure as well as rotor speed. The embodiment of FIG. 6 may bemodified so that indexes I and j are stepped through where j is an indexfor an inlet pressure and the calibration prediction function representsflow rate of the pump against both rotor speed and inlet pressure. Athird parameter could be added such that pressure difference is steppedthrough as well. The embodiments of FIG. 7 and FIG. 6 also differ inthat the calibration procedure in FIG. 7 may be followed during a usageof the system (such as a treatment).

To begin a usage such as a treatment, a pump, such as a push pump may beset by a controller at a rate selected to establish a predefined flow atS202. At S206, a complementary rotor rate is estimated from acalibration function stored by the controller or accessible to it insome fashion (e.g. stored on the cloud or a web site) to estimate a pullpump rate. At S208, a push-pull configuration is established betweenpumps whose flows are to be balanced or proportioned as describedherein. This configuration may be established by suitable operation ofone or more valves as described herein and in other embodiments capableof establishing a closed circuit between the two pumps, a flow imbalancebetween which may be detected. The controller may store multiplepreselected values of pump speed and pressure conditions or a series ofvalues may be computed according to a formula and these pressureconditions and pump speeds may be stepped through in a calibrationprocedure. This is the above-noted modification of the FIG. 6embodiment. Alternatively, as discussed with reference to FIG. 7, a newcommanded pump rate which is selected based on a production requirement(e.g., a treatment selection) is selected at S202 and the followingsteps are performed to calibrate at that pump speed (or in amodification, at a number of speeds near that pump speed). At S208, thepush pull configuration is established. At S209, selectable flowrestrictors are adjusted to establish a selected pressure condition(again, inlet pressure of one or both of the pumps or an outlet pressureof one or both of the pumps or a combination of any or all of these). AS210, the pull pump is run. This latter step may be done simultaneouslywith S209. At S212, the estimated value of the pull pump speed may bedynamically changed based on a proportional-differential controlalgorithm or some other algorithm until, using the accumulator pressuresensor, a match of the push and pull flows, within a predefined range,is established. In this embodiment or those described with reference toFIG. 6, the push pump speed may be altered to match that of the pullpump instead or both speeds may be modified to match each other. Thematch may be determined by seeking a control goal of zero rate of changeof accumulator pressure. During the S212, control may loop through S216to bail out of the PID control function if it is taking too long. Oncethe flow rates are matched, the function mapping the pressure conditionsand pump rotor speeds to flow is adjusted for the current conditions atS218 and the current selected flow rates established according to therevised function. If necessary depending on how or where the data arestored, the update may be stored elsewhere at S220, such as on a cloudstorage. At S214, the production mode continues until a period of timelapses, or a change in the condition of the production mode occurs suchas a lapse of time as indicated at S204.

The calibration procedure may be repeated by step S204 for a number ofdifferent conditions during a production run (e.g., treatment) orbetween consecutive production runs. Possible conditions include numberof rotations of a pumps rotor per the pump tubing segment or per thepump itself, or both, since the last calibration; the number ofocclusions of a roller per the pump tubing segment or per the pumpitself, or both, since the last calibration; total run time on the pumptubing segment or the pump, total time the pump tubing segment has beeninstalled on the pump, Any of these factors may be established accordingto temperature, temperature change between production runs or during aproduction run, maximum potential flow rate, a predefined allowed errorrate, temperature change, pressure change, etc.

At S212, one or more pressures (e.g., one or more of the pump inlet andoutlet pressures as described in the above-described figures) and thepull pump speed for the currently selected push pump speed are recordedby the controller. Next, at S116, the controller determines if furtherpump speeds of N pump speeds (N being a predefined number of pump speedsselected to cover a range of flow rates suitable for generating asufficiently accurate flow model of the pull pump speeds correspondingto any predefined push pump speeds) remain to be selected to complete acalibration operation. If further push pump speeds are to beimplemented, then a next push pump speed in a predefined schedule of Npump speeds is selected (S112) and the push pump speed is established bythe controller at S106. If the N^(th) push pump speed has already beenestablished at S116, then the controller takes the calibration data (allthe pressures and pump speeds recorded at S114) and generates a model byfitting the data. Alternatively, the calibration data may be stored andused directly or by interpolating or extrapolating to identify the pullpump speed that best corresponds to a balanced flow given a given pushpump speed.

FIG. 9 shows a flow balancing system that is substantially the same asdescribed with reference to FIGS. 2A through 2D and operable in the samemodes described in connection with respect to those figures. Theembodiment of FIG. 9 includes an active accumulator 745 in place of thefixed accumulator 138. The active accumulator has a pressure sensor 748that detects pressure in an interior volume 742 whose size is selectableby a piston 740 actuated by an actuator 723 under control of acontroller 766. Pressures into and out of the accumulator may bemeasured by respective pressure sensors 744, respectively. Duringcalibration, the suction head of the pull pump may be different from thesuction head of the pull pump during normal production mode operationbecause of the flow path change. Since peristaltic pumps are sensitiveto suction head variability, the volumetric efficiency of the pumpduring calibration may be different from that during operation which isundesirable. The controller can regulate the volume of the accumulatorso as to establish a predefined pressure at the pull pump and then usethe rate of change of volume indicated by the actuator 723 displacementas an indicator of the mismatch in flow rate rather than the pressure ofthe accumulator. Thus, the synchronization process is fed an errorindicative of the volume of the accumulator not the pressure.Synchronization may be performed otherwise as in any of the disclosedembodiments. Preferably, the active accumulator 745 is of such designthat its interior volume is precisely known given the displacement ofthe actuator 723. For example, a cylinder and piston arrangement ofstiff materials may be used.

FIG. 10 shows a method for calibrating one pump against another in whicha volumetric efficiency of one of the pumps is altered so as to speedthe matching of flow rates in a push-pull arrangement, according toembodiments of the disclosed subject matter. The graphs show acharacteristic pump curve correlating shaft RPM with flow for differentinlet pressures or “suction head.” In any of the embodiments, whenoperated in push-pull mode, the controller may choose suction head orvolumetric efficiency of pump so that the net flow rate into the branchdoes not coincide predefined pulse rate and/or phase relationships ofthe push and pull pump pulsatile flow that makes it difficult toconverge quickly and accurately to a synchronous pumping rate coincidingwith zero average net flow into the branch (i.e., equal flow rates ofthe push and pull pumps). In the illustrated example, the inlet pressureof one of the pumps has been adjusted to P3 with the other pumpremaining at P1 thereby creating a matching flow condition with aselected difference in the angular speeds of the pumps Δω₁ asillustrated.

FIG. 11 shows a method for calibrating one pump against another in whicha calibration is set up by controlling total flow so as to avoidconditions that are predicted to result in a slow speed of matching offlow rates in a push-pull arrangement, according to embodiments of thedisclosed subject matter. In the FIG. 11 example, instead of changingthe conditions of one of the pumps, the total flow rate is adjusted toavoid the difficult-to-synch condition identified with reference to FIG.10. In this case, the pumps may be non-identical and under certain flowrate conditions, the two pumps may produce a pulsatile pattern thatcauses the synchronization process to converge slowly due to, forexample, very slow beats which may introduce a sample bias in theaverage pressure estimation of the branch.

FIGS. 12A and 12B show multiple line peristaltic pump configurations inwhich the flow in two lines are adjusted relative to each other byrestricting flow into or out of the pumps by a control valve such thatthe flow can be matched, according to embodiments of the disclosedsubject matter. A single rotor 750 has multiple rollers 751, for examplethe eight shown. Two or more pumping tube segments 752 and 754 engagethe rollers for substantially balanced flow to and from a treatmentdevice. The flow of either line 752 or 754 may be adjusted independentlyof the other by adjusting a flow restriction on the inlet (760 and/or761) or the outlet (762 and/or 766) or both. In this way, pumping can besynchronized and calibration done according to the various embodimentsby changing a flow restriction rather than a pumping rate. In theembodiment of FIG. 12B, two different rotors 781 and 782 which may ormay not be driven by the same motor. In this embodiment, the flow rateis controlled by regulating flow restrictors 760 and/or 761 as in theembodiment of FIG. 12A. Outlet restrictors may also be provided. Anynumber of pumping tube segments or segment-rotor combinations may beused.

FIG. 13 shows properties of a peristaltic pump with a variable rotationrate, according to embodiments of the disclosed subject matter.Peristaltic pumps alternately pump and occlude as the rotor rotatesproducing a pulsatile flow. The variability of this pulsation be reducedby shorting the occlusion interval by increasing the rotor speed toshorten the occlusion interval. The variable speed rotation rate andvolume rate curves illustrate this for comparison between conventionaland variable speed. This may be implemented using a stepper motor, forexample. The point of occlusion can be detected by a pressure or flowsensor connected to a controller and used by the controller to regulatethe pump rate with angle of displacement to achieve the effect shown.

FIG. 14 illustrates a system and method of matching flows between pumpsfor purposes of calibration using a common flow path 825 according toembodiments of the disclosed subject matter. Blood is pumped by bloodpump 812 through venous 828 and arterial blood lines through a dialyzer804. Fluids 832 and 830 are pumped through the dialyzer 804 through line820 by pump 822 and 806 and removed from the dialyzer 804 by pump 819.To synchronize pump combination 806 and 822 with pump 819, pump 819 mayflow through a common segment 825 with pressure sensors 828 and 827positioned to measure a pressure drop therealong. The flow path throughthe common segment 825 may be defined by the controller which may setcontrol valves 801, 802, 803, and 804 to flow fluid from 832 and 830through the common segment 825 and then flow from the dialyzer 824through the common segment 825 at separate times.

During treatment, the flow may be as indicated by arrows 842 and 844.During a first calibration mode, pump 806 is not run and flow from pump822 passes through valve 801 though valve 802 through common segment825, through valve 803 and out through waste line 818. The pressure dropin the common segment 825 as indicated by pressure sensors 828 and 827is recorded. This may be repeated for several flow rates at a singletime. The first calibration mode may be instantiated at times duringtreatment, during a priming operation, after manufacturing, or at othertimes. The instantiation during treatment may be triggered by variousevents as identified below. During a second calibration mode flow frompump 806, pump 822 is not run and flow passes through valve 801 thoughvalve 802 through common segment 825, through valve 803 and out throughwaste line 818. The pressure drop in the common segment 825 as indicatedby pressure sensors 828 and 827 is recorded. This may be repeated forseveral flow rates at a single time. The second calibration mode may beinstantiated at times during treatment, during a priming operation,after manufacturing, or at other times. The instantiation duringtreatment may be triggered by various events as identified below. Duringa third calibration mode flow from pump 819 passes through valve 805though valve 802 through common segment 825, through valve 803 and outthrough waste line 818. The pressure drop in the common segment 825 asindicated by pressure sensors 828 and 827 is recorded. This may berepeated for several flow rates at a single time. The third calibrationmode may be instantiated at times during treatment, during a primingoperation, after manufacturing, or at other times. The instantiationduring treatment may be triggered by various events as identified below.During a fourth calibration mode, both pumps 806 and 822 may be operatedsimultaneously with suitable settings of the valves to cause the flow topass through the common segment 825. Any combination of thesecalibration modes may be instantiated at various times as indicated. SeeFIG. 20 for an example method embodiment which is applicable to any ofthe embodiments disclosed herein.

The pressure drop data captured during the calibration instances may beused to adjust stored pump functions that relate pressure, flow, andpump axis speed as discussed elsewhere herein. Note that the calibrationmay be based on a common reference pump and all the other pumps may becalibrated to that standard. This bases the accuracy of all the pumpsdependent on the accuracy of the reference pump. But the accuracy of thepumps relative to each other can be much greater. In dialysis treatment,the rate of flow of dialysate can vary by 10% but it is desirable forthe accuracy of differential flow, upon which ultrafiltration is based,to be much more accurate than that. Examples of reference pumps are anyof the pumps in the system. Note that more than one reference pump maybe used in a single embodiment.

Note that although the embodiment of FIG. 14 shows two fluid sources 826and 828, other fluids could be added or one of these two could besubtracted to form new embodiments. Also, the fluids could be used forpredilution or post-dilution of blood, for drug or medicament infusioninto blood, or for various other purposes as described in connectionwith the various embodiments. It should be clear from the above thatthere is a benefit to flowing fluid through the exact same common tube825. This eliminates any error due to difference in the size or otherproperties of the tube 825 thereby ensuring more accurate pressure dropdata.

The common segment 815 may be calibrated with a standard solution suchas blood normal saline in order to obtain a flow vs. pressure dropcurve. Thereafter, the flow can be calculated based on the flow vs.pressure drop curve for calibration of pumps. The curve data may begenerated for multiple temperatures and multiple fluids. The commonsegment 825 may be made of a durable material with consistent mechanicalproperties. Upon manufacture, the common segment 825 may be permanentlysealed to a fluid circuit to complete manufacture thereof.

FIG. 15 illustrates a system with a common segment 830 configured insuch a way that the pressure loss of fluid as it flows through thecommon segment 830 can be obtained without can be used without wastingfluid. The ingoing pump or combination thereof (e.g., 806, 822 and/orothers) can be directed by valves 810 and 808 to flow through the commonsegment 825 as indicated by arrow 855 at first times. The outgoing pumpor combination thereof (e.g., 819 and/or others) can be directed byvalves 815 and 812 to flow through the common segment 825 as indicatedby arrow 856 at second times. The pressure drop data acquired may beused as discussed with reference to FIG. 15.

FIGS. 16 through 19 illustrate systems for conserving treatment fluidused for calibration according to embodiments of the disclosed subjectmatter. In FIG. 16, a branch channel 915 serves the same function as in154, 441 in prior embodiments and others described but not shown infigures. Unlike the earlier embodiments, during calibration, the flowthrough the branch channel 915 is recovered after it flows through thepull pump 912 through a line 911 where it is flows into the treatmentdevice 904. An accumulator 960 may be provided. A pressure sensor 962may also be provided. These serve the same functions described above andelsewhere herein, namely, to synchronize flow between pumps 920, 934,and/or 912 calibrated against a reference one of the pumps 920, 934, or912.

During treatment, pump 920 and 934 pump fluid into a fresh medicamentline 925 through valves 908 and 909. The fluid passing into freshmedicament line 925 passes through the treatment device 904 to a spentmedicament line 905, through the valves 911 and 936 pumped by pump 912.Finally spent medicament is discarded through a spent medicament wasteline 932.

During respective calibration procedures, fluid may be pumped by pump920 and/or 934 through the branch line 915 through pump to synchronizewith pump 912 and then pass out through the spent medicament waste line932 where it is discarded. The calibrating flow may be established byvalves 909, 911 and 936 and the operation/non-operation of the pumps 920and 934 such that one or both of pumps 920 and 934 are in push-pullrelationship with pump 912. Initially, upon establishment of acalibration instance, valve 936 may send fluid from a pumping channel929 between valves 911 and 936 out through spent medicament waste line932 until fresh medicament clears the pumping channel 929. This may bedetermined by the controller 966 as the passing of a sufficient volumethrough it upon instantiation of the calibration responsively to flowrate and time. After an interval during the respective calibrationprocedure, the interval being long enough for spent medicament to clearthe pumping channel 929 between valve 911 and valve 926 (which may belonger than the minimum required for certainty that spent medicament isflushed), the valve 936 may set to convey fluid through fresh medicamentline 911 through valve 908, which may be set to convey the freshmedicament to the treatment device 904. In this way, the quantity offresh medicament used for calibrating can be minimized.

The configuration of FIG. 16 may be suitable for online medicamentgeneration (embodiment of source 928) such as provided in dialysateclinics. The configuration of FIG. 17 may be suitable for medicamentsupplied using a container (embodiment of source 928). In FIG. 17, abranch channel 915 serves the same function as 915 of FIG. 16 andprevious figures (e.g. 154, 441) in prior embodiments and othersdescribed but not shown in figures. As in the embodiment of FIG. 16,during calibration, the flow through the branch channel 915 is recoveredafter it flows through the pull pump 912 through a line 907 where it isflows into a source container embodiment of source 928 therebyrecovering it.

An accumulator 960 may be provided. A pressure sensor 962 may also beprovided. These serve the same functions described above and elsewhereherein, namely, to synchronize flow between pumps 920, 934, and/or 912calibrated against a reference one of the pumps 920, 934, or 912.

During treatment, pump 920 and 934 pump fluid from sources 926 and 928into a fresh medicament line 907 through valves 908 and 909. The fluidpassing into fresh medicament line 907 passes through the treatmentdevice 904 to a spent medicament line 905, through the valves 911 and936 pumped by pump 912.

During respective calibration procedures, fluid may be pumped by pump920 and/or 934 through the branch line 915 through pump to synchronizewith pump 912 and then pass out through the spent medicament line wasteline 932 where it is discarded. The calibrating flow may be establishedby valves 909, 911 and 936 and the operation/non-operation of the pumps920 and 934 such that one or both of pumps 920 and 934 are in push-pullrelationship with pump 912. Initially, upon establishment of acalibration instance, valve 936 may send fluid from a pumping channel929 between valves 911 and 936 out through spent medicament waste line932 until fresh medicament clears the pumping channel 929. This may bedetermined by the controller 966 as the passing of a sufficient volumethrough it upon instantiation of the calibration responsively to flowrate and time. After an interval during the respective calibrationprocedure, the interval being long enough for spent medicament to clearthe pumping channel 929 between valve 911 and valve 926 (which may belonger than the minimum required for certainty that spent medicament isflushed), the valve 936 may set to convey fluid through fresh medicamentline 907 to the source 928, which may a container or a manifoldconnected to multiple containers. In this way, the quantity of freshmedicament used for calibrating can be minimized.

The configuration of FIG. 18, like the configuration of FIG. 16, may besuitable for online medicament generation (embodiment of source 928)such as provided in dialysate clinics. In the embodiment of FIG. 18, abranch channel 915 serves the same function as 915 of FIG. 16 andprevious figures (e.g. 154, 441) in prior embodiments and othersdescribed but not shown in figures. During calibration, the flow throughthe branch channel 915 is recovered after it flows through the pull pump912 through a line 957 where it is flows into a recovery container 940where it is stored until the collected medicament therein can be pumpedby the pump 920 by selecting a corresponding position of the valve 955.The valve 955 may be controlled to select either an online source 928(or other source, such as a container embodiment) or the recoverycontainer 940 depending on the fill status of the recovery container940.

An accumulator 960 may be provided. A pressure sensor 962 may also beprovided. These serve the same functions described above and elsewhereherein, namely, to synchronize flow between pumps 920, 934, and/or 912calibrated against a reference one of the pumps 920, 934, or 912.

During treatment, pump 920 and 934 pump fluid from sources 926 and 928into a fresh medicament line 907 through valves 908 and 909. The fluidpassing into fresh medicament line 907 passes through the treatmentdevice 904 to a spent medicament line 905, through the valves 911 and936 pumped by pump 912.

During respective calibration procedures, fluid may be pumped by pump920 and/or 934 through the branch line 915 through pump to synchronizewith pump 912 and then pass out through the spent medicament line wasteline 932 where it is discarded. The calibrating flow may be establishedby valves 909, 911 and 936 and the operation/non-operation of the pumps920 and 934 such that one or both of pumps 920 and 934 are in push-pullrelationship with pump 912. Initially, upon establishment of acalibration instance, valve 936 may send fluid from a pumping channel929 between valves 911 and 936 out through spent medicament waste line932 until fresh medicament clears the pumping channel 929. This may bedetermined by the controller 966 as the passing of a sufficient volumethrough it upon instantiation of the calibration responsively to flowrate and time. After an interval during the respective calibrationprocedure, the interval being long enough for spent medicament to clearthe pumping channel 929 between valve 911 and valve 926 (which may belonger than the minimum required for certainty that spent medicament isflushed), the valve 936 may set to convey fluid through fresh medicamentline 907 to the recovery container 940. In this way, the quantity offresh medicament used for calibrating can be minimized.

The configuration and operation of the embodiment of FIG. 19 is similarto that of FIG. 18, except that there is no recovery container in a line959 such that during calibration, a closed loop may be formed wherebyfresh medicament recirculates in channels 959, 909, 915 and 929 once thepumping channel 929 is cleared after initiation of the calibrationprocedure. Note that an accumulator may be included in the line 959 tomitigate pressure interaction between the pumps 920 and 912.

In variants of the embodiments of FIGS. 17, 18, and 19, if pump 930 isdesired to be calibrated against pump 912, the fluid in source 926 maybe passed through medicament waste line 932 and discarded, duringcalibration. In these embodiments, medicament may be recovered duringcalibration of pump 920. In the embodiments of FIGS. 16-19, allreferences to medicament may be replaced by drug or infusate or otherdescriptor in alternative embodiments as it should be clear theembodiments are not limited to the particular fluids identified in thedescription of the operation and configuration.

Referring to FIG. 20, a general flow system 978 has a fluid source, achannel that may have a component 981 therealong, and a fluid receiver984 which may or may not be the same as the source 980. All of these areconnected by a fluid channel 985 and pumped by peristaltic pumps 982 and983. In embodiments, the fluid carried by the system is any fluid. Infurther embodiments, the fluid is aqueous. In further embodiments, thefluid is incompressible. It should be evident the previous embodimentshave the characteristics of the system of FIG. 20 during production ortreatment mode. In embodiments, the component 981 permits the flow ratesof the two pumps 982 and 983 to differ, for example, if it is adialyzer, there may be a net fluid flow into or out of the component981. In the embodiment, it is desired to have a predefined relationshipbetween the flow rates created by the two peristaltic pumps 982 and 983.This relationship may be maintained by controlling the rates of thepumps 982 and 983. However, peristaltic pumps 982 and 983 it may not bepossible to determine the rate of flow by controlling the flowconditions of peristaltic pumps 982 and 983, for example their inletpressures and shaft speeds, since these may change during operation,vary due to manufacturing variability, and other factors. Thus, flowsensors may be used such as flow sensors 986 and 987. Flow sensors 986and 987 may be used to measure flow into component 981 and out ofcomponent by sampling and averaging over a time window in order toobtain a time-moving average that may be used to control the speeds ofthe pumps to maintain the desired flow ratio and net volume transferredinto or out of the component 981. Alternatively, as described withembodiments herein-described, a branch channel 992 may be selectivelyinterposed by valves 989 and 990 under control of a controller. In thistemporary calibrating flow configuration, as discussed elsewhere, theflow rates of the pumps are actively matched using a pressure signal inthe branch channel 992. There may be no need for the flow sensors 986and 987.

In the system 978, in the production (or treatment) or calibratingconfiguration, the peristaltic pumps 982 and 983 can interact in such away as to cause instability in the flow which can cause the flow to benon-repeatable or such that a computed sum of the individual flow rates,predicted by the rotation speed (even if derived from a calibration) ofthe two peristaltic pumps 982 and 983 departs substantially from the netflow rate when the two peristaltic pumps 982 and 983 are connected asshown. It has been found that this variability can be minimized byoperating such that a substantial difference in the frequencies of thepulses produced by the two peristaltic pumps 982 and 983 is alwaysmaintained during operation. For example, in a dialysis system, wherethe component 981 is a dialyzer and nearly equal flow rates are desiredto be maintained in the two pumps to produce a balanced inflow andoutflow to/from the component 981, the two peristaltic pumps 982 and 983may have a different number of rollers. Alternatively, the pumping tubediameters used with identical peristaltic pumps 982 and 983 may bedifferent from each other sufficiently to ensure the frequencydifference. In other embodiments, the suction head of the pumps may beselected using a flow resistance to ensure the frequency difference.

In embodiments, the system of FIG. 20 operates over a predefined rangeof flow rates and the combination of pump tube diameters, number ofrollers, and suction side flow resistances of the pumps are such that,over substantially all of the predefined range of flow rates, the pulserates of the pumps are different and they are never operated during anoperating function where the flow balance is required, such that thefrequencies are within 5% of each other. In embodiments, the ratio ofthe inverse of the difference between the pulse frequencies of the pumpsis multiple times the calibration interval. In embodiments, the ratio isalways greater than 3 times the calibration interval. In embodiments,the ratio is always greater than 5 times the calibration interval. Inembodiments, the ratio is always greater than 8 times the calibrationinterval. In embodiments, the ratio is always greater than 12 times thecalibration interval.

In the embodiments of FIG. 20, the fluid circuit connecting the pumpsmay lack a pressure dampening device such as one or more chambers in thefluid circuit. It has been demonstrated that pressure pulses can besubstantially mitigated by dampeners but this adds considerable cost toa disposable fluid circuit. The flow predictability features of theforegoing can be implemented with a lower cost disposable fluid circuitthan one that includes dampers.

As described in the various embodiments, a net flow into or out of acomponent, such as a dialyzer, filter, or other treatment device or afluid circuit component, the disclosed embodiments permit the adjustmentof a calibration of a pump to achieve a desired ratio of the ingoing andoutgoing flows to/from the dialyzer, filter, or other treatment deviceor a fluid circuit component. As described, the calibration may beperformed at predetermined times during a treatment or other type ofproduction operation. Once a pump is recalibrated, the change in thenumerical calibration data required to adjust the prediction of the flowrate from the axis speed and pump pressure conditions (inlet and/oroutlet pressure) may provide a means for estimating a magnitude of theerror in the net flow into or out of the component before theadjustment. This provides an opportunity for the control system tocompensate that error based on the estimate, thereby improving theoverall control of the system. Even if a pump's calibration data driftsfrom its prior calibration significantly, it may be possible tosufficiently compensate the consequences of that error that overall netflow into or out of the component, for the entire treatment or othertype of production, achieves its target. In extracorporeal bloodtreatment or peritoneal dialysis treatment, this means the net waterremoved from, or added to, a patient may be closer to the target. Thistechnique may be performed by any and all of the embodiments disclosedherein.

In embodiments, to use new calibration data and previous calibrationdata to compensate net inflow/outflow, the controller may adjust theparameters of calibration formula that gives flow volume as a functionof suction head and pump speed (RPM). This could represented by, forexample, a suitable quadratic surface such as Q=aω(bPi2+cPi) or a lookuptable that is linearly or curvilinearly interpolated/extrapolated. In anembodiment, the target flow rates may be calculated from the previousand adjusted model and the actual total displaced volume calculatedbased on the assumption of a linear change in the flow rates over theinterval between the calibrations. This effectively determines, based onthe assumption of a linear change over time of the actual flow rateversus the flow rate assumed by the model as it was from the lastadjustment at the start of the interval. From this, the cumulative errorin the net flow into the component or out of the component during theinterval can be determined. The future pumping rates may then beadjusted to correct the defect in the cumulative flow such that a targetcumulative volume into or out of the component is achieved by the end ofthe process. In embodiments, the ratio of flow rates of the net inflowpumps and net outflow pumps may be adjusted to take into account thecorrected cumulative volume transferred. Note that the adjustment forintervals during which the pumping rate has changed can be done bykeeping a record of the flow rate changes over the interval betweencalibrations and calculating at each change point, the difference in theflow estimated by the assumption of linear progression of the error andthe assumed error based on the calibration at the start of the interval.In an embodiment, the cumulative net flow into or out of the componentat each calibration during a production period may be calculated basedon an assumed linear change (note that the interpolation could haveother forms, such as quadratic or any other smooth or non-smoothfunction, based on theoretical or experimental data) in the flow rateper the corrected model and the assumed flow rate at the time the modelwas last corrected by calibration. Then, toward the end of theproduction operation, a single correction operation such as a bolustransfer to or from the component may be performed.

FIG. 21 illustrates the interpolation technique described above in theform of a flow rate vs. time graph for predictions of flow rate based ontwo calibrated models of flow rate and an interpolated model based onboth. Two calibrations are performed during a single operation such as adialysis treatment at respective points in time. At a point between thecalibrations, the flow rate (Q′) is stepped up. The lines represent theinstantaneous flow rate out of the component (e.g., dialyzer) calculatedper the calibration 1, the instantaneous flow rate out of the component(e.g., dialyzer) calculated per the calibration 2, and the instantaneousflow rate out of the component (e.g., dialyzer) according to a linearinterpolation representing a corrected instantaneous flow rate. From theinterpolated curve, the cumulative error can be calculated as shown bythe shaded area. The interpolation may be based on, for example, thelinear interpolation of coefficients of a polynomial or otherrepresentation of the pump characteristics so the shape need not bestraight lines as shown.

Note in all the embodiments in which a change in pressure is measured,or a change in pressure drop, the unsteady pressure change may bederived by various numerical methods from sampled pressure data. Anaveraging window may be used such as a triangular window or a Gaussianwindow. The window size may be selected for the particular function. Forexample for flow synchronization some variability in the averagedpressure may be tolerated. For a stored representation of pressure dropas in the embodiment of FIG. 14, a larger averaging window may beemployed to obtain a single pressure or pressure drop representative ofa point in time or interval of time.

In the foregoing it was assumed the push pump speed was established andthe pull pump speed was determined to match the push pump speed, but itshould be clear that in alternative embodiments, the pull pump may befirst selected and a matching push pump speed determined in S110. Notealso that the calibration procedure may be applied to multiple pushpumps in push-pull relation to one or more pull pumps. This increasesthe dimensionality of the model Q=f(P_(i,j), ω_(pull,i)) and thecombination of pumping speeds to be established but otherwise followsthe same operations described above. The model may be formed andcalibrated to provide a flow rate that is proportional (approximatelyequal) to the flow rate of the tandem pump.

Note that in any of the embodiments, the rotor speed of pumps can varywith phase angle and it will be understood that the referenced speed ofthe embodiments may be understood as an average speed taken overmultiple full rotations, RMS rotational velocity, or some otherstatistic or representation of the rotor's rate.

It should be clear that the methods, devices, and systems for balancingflows are applicable to any type of flow balancing application in whichfluid flows are desired to be balanced or proportioned in same mannerincluding medical and non-medical applications.

Although in the examples herein, fluid balancing devices, methods, andsystems were described in application to dialysis and extracorporealblood treatment, the same may also be applied to the balancing of otherphysiological fluids such as in peritoneal dialysis, apheresis,hemodiafiltration, hemofiltration, hemodialysis, liver dialysis, etc.Also, the principles are applicable to balancing system of any type inwhich net flow into or out of a component is desired to be maintained,including zero flow.

Although in the above embodiments, the flow of non-blood fluids isregulated to regulate transmembrane pressure, and thereby convection offluid across the filter membrane, it is also possible to regulate theblood side flow to achieve a similar result, in embodiments. Forexample, blood side flow may be regulated by ingoing and outgoing bloodpumps whose flow balance may be calibrated and/or confirmed by a commonflow meter or pressure sensor as in the above embodiments. FIG. 8illustrates an example of such a variant. A 502 filter 604 receivesblood via blood arterial 626 and venous 628 blood lines. The flow ofblood and transmembrane pressure in the filter 604 is regulated by thepumping rates of blood pumps 611 and 612. Blood flow can be selectivelydiverted through a branch line 625, with an accumulator 614 and pressuresensor 615, by control valves 610 under control of a controller 666.Medicaments 630, 632 such as dialysate, citrate, drugs, or other fluidscan flow through line 620 into the blood or the non-blood compartment offilter 604 from the various sources 630 through 636, each at ratesdetermined by respective pumps 606, 608, 622 or directly into the bloodfrom sources 634, 636 for pre and post-dilution of blood under controlof pumps 602 and 608 respectively. Various pressure transducers may bepositioned in the system to indicate one or both of upstream anddownstream pressures in order to permit prediction of the flow rates ofthe pumps based on shaft speed to be refined. The net fluid balanceunder all conditions can be maintained by regulating the pumping ratesof the blood pumps 611 and 612 because there is only one non-blood sidepump thereby allowing transmembrane pressure to be mediated by the bloodside. The pumping rates of non-blood fluids can be predictive asdisclosed above.

In the same or additional embodiments, the active accumulator can beused with pressure sensing as in the fixed accumulator embodiments.However the volume can be adjusted to compensate for the overall flowrate through the branch channel thereby making the rate of net flow intoor out of the accumulator more for synchronizing at different flow ratessimilar. So when synchronizing pumps flowing at low flow rates, theaccumulator volume may be low. When synchronizing pumps flowing at highflow rates, the accumulator volume may be adjusted to be higher.

As described, in any of the foregoing embodiments, the indication offlow difference between balancing pumps may be indicated by a flow orpressure signal during a calibration (or balance confirmation) flowconfiguration and procedure. For example, pressure rise or fall may bedetected when flow runs through a branch line. It is desirable to makethe detection of the flow synchronization as rapid as possible. However,minor variations in the pumping flow rates or pressures are overlayed onthe average flow or pressure due to inherent pulsing of certain types ofpumps, for example peristaltic pumps. This effect is exacerbated whenmultiple pumps are operating in series, both of which can affect theflow or pressure. The worst level of interference is when the pumps areoperating at close to the same speed and in a pressure- orflow-reinforcing phase relationship. The resulting beats can cause anenhancement of the sample bias resulting from a limited detectioninterval. For example if the pressure is sampled over only a fraction ofa beat, one of the other of the pressure peaks (mutually reinforcingcycles) or troughs (mutually destructive cycles) may contributedisproportionately to the average signal. This can occur even when anaverage is taken over multiple beats, where the number of beats issmall, for example, less than 5. Of course a very long sampling intervalcan avoid this problem, but it is preferred to achieve an accuratepressure indication in a short time.

In the various embodiments, the branch channel leads to a drain. Fluidotherwise directed to a dialyzer or hemofilter or other treatment devicecan be selectively diverted through the branch channel to the drain forother reasons besides the pump synchronization, providing a doublefunction. For example, if a fluid anomaly such as temperature or air isdetecting in the fluid heading for the dialyzer, it could be diverteduntil the anomaly clears. This may facilitate priming of the dialysateside of the dialyzer.

In the various embodiments, two pumps are used for flowing dialysateinto and out of the dialyzer (or equivalent for other types of treatmentdevices). The pumps may operate in either direction. This allows primingto be performed on the blood and dialysate sides of the treatmentcircuit at the same time. According to embodiments, the two dialysatepumps include an inflow pump and an outflow pump, two outflow pumps, ortwo inflow pumps, depending on the controller's selection of speed androtational direction (so either pump could play either role). Inembodiments, priming may be done by pumping dialysate such that the pumprate out of the filter is lower than the pump rate in to the filter orboth pumps may be operated in an outflow mode such that the net rateinto the filter is such that dialysate is forced through the membraneinto the blood circuit. In other embodiments, fluid can be drawn from afluid source connected to the blood circuit by dialysate pumps that pullfluid through the membrane into the dialysate side, thereby, again,priming both sides of the circuit. In this latter embodiment, the inflowand outflow pumps may operate to different rates to generate a net flowfrom the blood side to the dialysate side or both pumps may operate inan outflow mode.

In all the various embodiments, a valve can be provided in the spentdialysate path to return fluid that is used for synchronization to arecovery channel where it may be used for treatment rather than wasted.A vessel may be used to hold recovered dialysate in online dialysatesystems or recovered dialysate may be flowed into a container for baggeddialysate setups.

To mitigate the sample bias that attends operating multiple pumps suchthat they mutually interfere to reinforce or cancel pressurefluctuations, any of the embodiments may include the additional featuresas follows.

1. The pump tube segments of the respective pumps (or pumping tubesegments as appropriate for the type of pump embodiment) that contributeto the pressure in the accumulator may be chosen to have differentdiameters selected to ensure that the pressure pulse rates theycontribute are substantially non-synchronous over the range of predictedflow rates. For example, the pressure pulses of one pump, at a worstcase condition, may be at least 2 times that of any other. Alternativelyanother predefined multiple may be used (other than 2). As aconsequence, pumps that operate at similar flow rates, different tubingdiameters of peristaltic pumps would require one pump rotor to turn at adifferent rate than the other thereby avoiding the reinforcing effect.

2. For peristaltic pumps, the numbers of rollers of peristaltic pumpsmay be selected such that the reinforcing effect is reduced. Forexample, the dialysate pumps (or blood pumps of FIG. 8) may havedifferent numbers of rotors, since these pumps pump fluid at close flowrates. Obviously pumps that operate normally at very different rates donot produce the reinforcing effects if the number of rollers or tubingdiameters are similar so the requirement may be to choose tubingdiameters and roller numbers to ensure the reinforcing effect isminimized, or more broadly stated, choosing number of rollers and/orpump tubing segment diameters responsively to the pulsing rate of therespective pumps. A configuration may be provided such that the pressurepulses of one pump, at a worst case condition, are at least 2 times thatof any other as a result of one or both of the number of rollers and/orthe diameter of the respective pump tubing segments. Alternativelyanother predefined multiple may be used (other than 2).

3. The controller may be programmed to select operating conditions thatavoid the sample bias effect. Thus, in programming the controller, theoperating states associated with the condition of excess sample bias maybe predicted and stored in the controller. Alternatively, a numericalmodel of the system may be stored in the controller that predicts thesample bias or data responsive to the sample bias with an optimizationalgorithm that seeks an operating state that has the largest pressurepulse rate difference for those pumps contributing to pressure in theaccumulator (e.g. 412). The goal state of such an optimization algorithmmay simply be vectors representing a predefined range of the multipleand the targeted flow rates of the respective pumps. To support thecontrollers freedom to select a flow rates according to treatmentoperation requirements while still avoiding operating states with highsample bias, one or more pumps or flow channels can have selectable flowrestrictors or peristaltic pump occlusion to selectively change thevolumetric efficiency of the pumps whereby the relationship between RPMand flow rate for a given suction pressure head is changed making thevolumetric efficiency of one pump different from the other (i.e., volumedisplaced per revolution).

4. In any of the foregoing embodiments, the pumps may have a fixed ratioof pressure pulses, for example by attaching the pump rotors to a commonshaft, while managing the pumping rates by regulating an active flowrestrictor upstream or downstream of one or more of the pumps in orderto control the relative flow rates of the pumps. The fixed ratio may beselected at design time and it may remain constant for all operatingconditions, according to this scheme.

5. The same scheme as number 4 may be implemented using active controlto ensure a predefined ratio of rotor speeds rather than a mechanicalinterconnect between the rotors.

6. In any of the embodiments, the pumps in a push-pull arrangement maybe run at rates that produce identical flow pulse frequencies whilestill adjusting the net flow rate into the branch channel (accumulatorand branch line) changing the volumetric efficiency of one of the pumpsby restricting flow upstream of one of the pumps. This allows the flowrates to be synchronized while maintaining identical flow rates of thetwo pumps. This can be done with separate pumps controlled to run at thesame pulse frequency or by mechanically interconnected pump rotors (SeeFIGS. 12A, 12B, and 13 and related discussion, for example). Preferablythe down-regulated pump experiences an increased flow restriction at itsinlet since peristaltic pumps are more readily and precisely regulatedby upstream flow restriction.

7. In the scheme of 6, the pumps may be operated so that they remain inprecisely a phase difference such that their flow pulsations aremutually canceling, with the pulling pump drawing at the same time asthe pushing pump is pushing and with both pumps constricted at the sametimes. In this way the pulsations in the branch channel are minimized.

8. Each time a calibration is done, it can be done at one or moredifferent inlet and, optionally, outlet, pressure conditions that coverthe ranges of variability that the system may experience due tomanufacturing variability, setup variability, mechanical changes in thehardware components, and any factors that may cause differences in theinlet and outlet pressures or causative flow restrictions experienced bythe pumps. The different pressure conditions can be created by flowrestrictions in combination with the selection of pump speed usingfeatures as discussed herein.

The accuracy of the pump calibration/synchronization procedures andsystems described herein can be undermined by variability or faults indisposable parts and the proper mechanical operation of the machinery.For poor engagement of a pumping tube segment in a peristaltic pump maycause a lack of repeatability or unreliable operation of the pump. Toensure the integrity and accuracy of the procedures and devicessupporting synchronization, various devices and methods may be employedalone or in combination with any of the embodiments. Any of theseindications can be used to halt operation or to generate an alarm usingthe system controller of any of the embodiments. The following areexamples.

1. Measuring pressure at various points along the circuit to detectanomalous pressure changes indicating occlusion of a line.

2. Measuring pressure into and/or out of pumps to detect improper pumpfunction.

3. Pressure on peristaltic pump shoe, for example by means of one ormore strain gauges, the force exerted through the pump tube segment bythe rotor can generate a force temporal pattern or average that mayindicate incorrect setup or some other problem with the pump.

4. Acoustic or vibration detection on the pump or any of the tubingsegments may be used to indicate an anomalous operation ormisconfiguration.

5. One of the pumps to which other pumps or combinations are slaved bythe synchronization calibration procedures may be tested for flowcalibration using an independent flow measurement such as time-of-flightof a label such as temperature, composition property such as salinity,or air. See examples of this type of flow measurement in US PatentPublication 20150005699.

6. The same as 5 but applied to all the pumps to determine whether anyare out of bounds.

7. Air detection at any points in the fluid circuit where air should notbe present.

8. Position encoders on all control valve actuators to ensure full rangeof motion and speed of operation.

9. Force detection for control valves using a strain gauge on theactuators driving valve pinching elements.

10. Position encoding to detect full engagement of disposable with pumpand valve actuators.

11. External leak detectors such as water detection or resistivitysensors so that water leaking from engaged tubing sets will be detected.

12. Using the same sensor in a funnel configuration to detect bloodleaks as well as non-blood fluid leaks.

13. Temperature sensors in the fluid circuit to detect temperatureanomaly.

14. During priming, the blood pump may be run to force priming fluidthrough a dialyzer into the treatment fluid circuit. Pressure sensors inthe treatment fluid circuit may detect, and thereby verify, theconnections of the treatment fluid to the dialyzer thereby.

Note that in any of the embodiments, where a flow meter is used todetermine the flow rate, a precise flow restrictor with upstream anddownstream pressure sensors, or a pressure differential sensor acrossthe segment, may be used to measure the flow rate. Such a device, as isknown, for given fluid properties, can be used to measure flow rate. Inthe present application, such a device may allow flow to be measure inan inexpensive disposable so a novel benefit may arise. Thesynchronization of any of the method or system embodiments may beaccomplished without the use of an accumulator by programming thecontroller to flow each pump in turn through the flow restrictor,measuring the flow, and then switching in another pump. This may be donefor multiple flow rates.

Note that in any and all embodiments, instead of the controllerregulating the flow by changing the pump rotor speed, selectable flowrestrictors or recirculation channels may be used with a fixed pumprotor speed to selectively regulate flow. Such variations may help tomitigate the pulse reinforcement effect described immediately above. Inembodiments, the pumps may be operated such as to permit the phaserelationship to be controlled by the controller or mechanically-fixed(e.g., pump rotors on the same shaft). Where the pumps are controlled torun at the same speed, with flow rate regulated by controlling the inletor outlet pressure (i.e., pump head) or by using a selectable bypassrate, the pressure or flow pulses can be regulated by adjusting thephase such that the pressure or flow pulses cancel at the point ofmeasurement.

In any of the embodiments, a virtual pressure-based synchronization canbe performed. In the embodiments, the flow sync system pump rates areadjusted to match by detecting pressure in a branch channel. Inalternatives, the flow synchronization operation is performed butneither pumping rate is slewed. Rather the rate of change of thepressure (or volume of the active accumulator is detected and used tomake numerical compensation to the commanded pumping rates.

In any of the embodiments, virtual pressure compensation may beperformed. In most embodiments, pressure-dependent gains are applied toadjust pumping rates to compensate changes in inlet pressure. As analternative, the same pressure signals can merely be tracked/recorded,and used to make periodic adjustments to relevant pump rates at discreteintervals. The cumulative effect of pump inlet pressure changes over aprescribed period of time can be accumulated to calculate a “net volumeerror” for that time interval; rates for the next time interval can beadjusted to compensate for the previous interval's net pressure-basederror.

Note that in any of the embodiments, the passive accumulators may bereplaced with active device with a controllable interior volume. Thecontroller is programmed to seek and establish a predefined pressure inthe accumulator when the system is configured for synchronization, i.e.,the pumps are connected through the accumulator to test their pumpingrelationship. The predefined pressure may be chosen to minimize thepressure change experienced by each when the treatment/synchronizationswitchover occurs. The active accumulator pressure regulation may beaccomplished by means of a separate pump in communication with theaccumulator or by controlling one or both of the pumps being synched.FIG. 9 shows an example of an active accumulator 745.

In any of the foregoing embodiments, the controller may be configured toperform the synchronization at multiple pressure set points (pressureconditions at the inlets and outlets of the connected pumps) in order togenerate a dynamic pressure calibration curve that representssynchronized conditions at multiple pressure conditions. This isdiscussed above in embodiments, but it should be clear that the featureis applicable to any of the embodiments.

The synchronization process can be triggered, within a treatment cycle,on a predefined chronological schedule (every 15 minutes duringtreatment, for example) or upon the displacement of a calculated volumeof medicament (e.g. dialysate) or blood. Other trigger events are alsopossible.

1. The number of rotations of a pump actuator exceeds a predefinedvalue;

2. A change in fluid temperature or ambient temperature beyond apredefined magnitude; and

3. A change in pressure at any, or one or more predefined points in thesystem or a pressure differential at any point in the fluid circuit.

In any of the embodiments, the controller may be configured torecalculate or update the total accumulated ultrafiltrate of a treatmentcycle based on the changes in calibration generated from the synchingprocess.

In any of the embodiments, when a synchronization is done, one of thepumps may be identified as a master pump (one whose predicted pumpingrate is identified as true or accurate). In embodiments, the controllermay subject that master pump to an additional test in order to resetsits individual calibration by independently measuring flow against oneor more flow rate conditions. The resulting calibration data may be usedto adjust the prediction models for the master pump as well as the pumpwith which it was, or is going to be, synchronized. The independentmeasure of flow rate may be obtained using time of flight of a fluidlabel such as air bubbles injected and detected ultrasonically or atemperature label. An accurate flow meter may be used. Further fluidcircuit tests may be also be done to ensure the accuracy of thesynchronization process, for example, a pump occlusion test may be doneto ensure a predicted pressure rise occurs when a pump flow if blocked,line leaks may be detected, pressures in and out of the pump matchstored predefined values, for example.

In any of the embodiments, an active accumulator may be used to changethe total volume of the branch line that bypasses the device to bebalanced (e.g., a treatment device, dialyzer or any of the devicesidentified with the described embodiments in which a controlled inflowand outflow ratio is targeted), so that the rate of increase of pressuredue to the net inflow of fluid into the branch line and accumulator(total branch volume) together provides for rapid matching of the flowsinto and out of the branch line and stability of the control parametersused for matching. In an embodiment, a digitalproportional-integral-derivative control (PID control) method may beimplemented on the relevant controller.

In any of the embodiments, an accumulator may not need to be provided asa separate element in that natural compliance of the present fluidcircuit may be sufficient to allow calibration (synchronization) of theinflow and outflow pumps.

In any of the embodiments, including the claims, the calibration flowused for pump synchronization can be established in a same portion ofthe fluid circuit as used during treatment and thus flow does notnecessarily need to be diverted during calibration. For example, pinchclamps could be used to halt the flow of blood during calibration,including flow synchronization of the pumps, such that flow from thepumps governing flow into and out of a dialyzer (or blood treatmentdevice, hemofilter, patient interface or other terms equivalent to thedialyzer in terms of the calibration requirement) exists in a fixedvolume channel. As such, the pressure in the channel is determined byany difference in the flow rate thereby permitting synchronization andcalibration in a simpler arrangement. Similarly, the flow of non-bloodfluid such as dialysate can be pinched off (forming a direct channelbetween the two blood pumps (Such as the FIG. 8 embodiment) such thatthey can then be synchronized through the dialyzer. This eliminates theneed for branch line 625. Again as elsewhere the accumulator 614 wouldnot necessarily be needed.

According to first embodiments, the disclosed subject matter includes amedical treatment system. A first fluid management element pumps fluidfrom a patient interface device during a treatment. A second fluidmanagement element pumps fluid into a patient interface device during atreatment. A controller is connected to at least one of the first andsecond fluid management elements and has a processor programmed toregulate a rate of flow to or from the patient in order to achieve apredefined net removal of fluid from the patient during a therapeutictreatment implemented under control of the controller. A fluid circuitswitch allows a flow from the at least one of the first and second fluidmanagement elements to be selectively and automatically configured undercontrol of the controller between a therapy configuration for deliveringsaid therapeutic treatment to a calibration configuration in which flowthrough said at least one of the first and second fluid managementelements is temporarily diverted to a flow or pressure sensor thatoutputs a signal indicating a difference between the flow rates of thefirst and second fluid management elements that occurs during atreatment. The controller is programmed to calculate and store flowcorrection data representing a correction to be applied to a rate offlow of said at least one of the first and second fluid managementelements responsively to said signal. The controller is furtherprogrammed to modify a flow rate of said at least one of the first andsecond fluid management elements responsively to said flow correctiondata.

The first embodiments may be modified to form additional firstembodiments in which a diverted flow in the calibration configurationflows between the first and second fluid management elements through afluid accumulator connected to a pressure sensor that outputs saidsignal. The first embodiments may be modified to form additional firstembodiments in which an accumulator is configured such that pressureincreases as fluid fills said accumulator, whereby a difference in theflow rates of said first and second fluid management elements results inan increasing or decreasing pressure.

The first embodiments may be modified to form additional firstembodiments in which the accumulator has a residual volume of fluid topermit the measurement of a pressure change caused by a net removal or anet addition of fluid from or to said accumulator. The first embodimentsmay be modified to form additional first embodiments in which the firstfluid management elements include a peristaltic pump. The firstembodiments may be modified to form additional first embodiments inwhich the fluid circuit includes a disposable plastic tubing set and atleast one control valve. Here and in any of the embodiments, the atleast one control valve (or any control valve) can be made of lengths oftubing of the disposable plastic tubing set, which lengths are joined byat least one junction, such as a T junction or a Y junction, or a H, or4-way crossing junction. Any kind of junction may be used. The tubinglengths are engageable with pinch clamps that selectively seal thetubing lengths under control of a controller. The pinch clamps may bepermanent reusable elements of a system that pinch respective portionsof the tubing set to selectively form different flow paths.

The first embodiments may be modified to form additional firstembodiments that include a third fluid management element that pumpsfluid into the patient during a treatment, the third fluid managementelement being coupled to a synchronization mechanism that causes thefirst and third fluid management elements to pump equal amounts of fluidper unit time during a treatment. The first embodiments may be modifiedto form additional first embodiments that include a third fluidmanagement element that pumps fluid into the patient during a treatment,the third fluid management element being coupled to a mechanicalsynchronization mechanism that causes the first and third fluidmanagement elements to move in mechanical synchrony such that they pumpequal amounts of fluid per unit time during a treatment through thefluid circuit.

The first embodiments may be modified to form additional firstembodiments that include a blood circuit connected to the fluid circuitby a membrane. The first embodiments may be modified to form additionalfirst embodiments in which the flow or pressure sensor is a flow sensor.The first embodiments may be modified to form additional firstembodiments that include a blood circuit connected to the fluid circuitby a membrane and wherein a diverted flow in the calibrationconfiguration flows through a flow path between the first and secondfluid management elements through a fluid accumulator connected to apressure sensor that outputs said signal, wherein the membrane isseparated from the flow path. The first embodiments may be modified toform additional first embodiments in which the second fluid managementelement is connected to a source of a medicament.

The first embodiments may be modified to form additional firstembodiments in which the controller is connected to a user interface andprogrammed to accept and store ultrafiltration data representing atarget net ultrafiltration, wherein the controller is further programmedto control flow through said at least said one of said first and secondfluid management elements responsively to said ultrafiltration data.

According to second embodiments, the disclosed subject matter includesmedical treatment system. A first pump pumps fluid from a patientinterface device during a treatment. A second pump that pumps fluid intoa patient interface device during a treatment. A controller is connectedto at least one of the first and second pumps and has a processorprogrammed to regulate a rate of flow to or from the patient in order toachieve a predefined net removal of fluid from the patient during atherapeutic treatment implemented under control of the controller. Afluid circuit switch allows a flow from the at least one of the firstand second pumps to be selectively and automatically configured undercontrol of the controller between a therapy configuration for deliveringsaid therapeutic treatment to a calibration configuration in which flowthrough said at least one of the first and second pumps is temporarilydiverted to a flow or pressure sensor that outputs a signal indicating adifference between the flow rates of the first and second pumps. Thismay be done during treatment, during priming, or during calibrationoperations or testing. The controller is programmed to calculate andstore flow correction data representing a correction to be applied to arate of flow of said at least one of the first and second pumpsresponsively to said signal. The controller is further programmed tomodify a flow rate of said at least one of the first and second pumpsresponsively to said flow correction data.

The second embodiments may be modified to form additional secondembodiments in which a diverted flow in the calibration configurationflows between the first and second pumps through a fluid accumulatorconnected to a pressure sensor that outputs said signal.

The second embodiments may be modified to form additional secondembodiments in which an accumulator is configured such that pressureincreases as fluid fills said accumulator, whereby a difference in theflow rates of said first and second pumps results in an increasing ordecreasing pressure. The second embodiments may be modified to formadditional second embodiments in which the accumulator has a residualvolume of fluid to permit the measurement of a pressure change caused bya net removal or a net addition of fluid from or to said accumulator.The second embodiments may be modified to form additional secondembodiments in which the first pumps include a peristaltic pump.

The second embodiments may be modified to form additional secondembodiments in which the fluid circuit includes a disposable plastictubing set and at least one control valve. Here and in any of theembodiments, the at least one control valve (or any control valve) canbe made of lengths of tubing of the disposable plastic tubing set, whichlengths are joined by at least one junction, such as a T junction or a Yjunction, or a H, or 4-way crossing junction. Any kind of junction maybe used. The tubing lengths are engageable with pinch clamps thatselectively seal the tubing lengths under control of a controller. Thepinch clamps may be permanent reusable elements of a system that pinchrespective portions of the tubing set to selectively form different flowpaths.

The second embodiments may be modified to form additional secondembodiments that include a third pump that pumps fluid into the patientduring a treatment, the third pump being coupled to a synchronizationmechanism that causes the first and third pumps to pump equal amounts offluid per unit time during a treatment.

The second embodiments may be modified to form additional secondembodiments that include a third pump that pumps fluid into the patientduring a treatment, the third pump being coupled to a mechanicalsynchronization mechanism that causes the first and third pumps to movein mechanical synchrony such that they pump equal amounts of fluid perunit time during a treatment through the fluid circuit. The secondembodiments may be modified to form additional second embodiments thatinclude a blood circuit connected to the fluid circuit by a membrane.The second embodiments may be modified to form additional secondembodiments in which the flow or pressure sensor is a flow sensor.

The second embodiments may be modified to form additional secondembodiments that include a blood circuit connected to the fluid circuitby a membrane and wherein a diverted flow in the calibrationconfiguration flows through a flow path between the first and secondpumps through a fluid accumulator connected to a pressure sensor thatoutputs said signal, wherein the membrane is separated from the flowpath. The second embodiments may be modified to form additional secondembodiments in which the second pump is connected to a source of amedicament. The second embodiments may be modified to form additionalsecond embodiments in which the controller is connected to a userinterface and programmed to accept and store ultrafiltration datarepresenting a target net ultrafiltration, wherein the controller isfurther programmed to control flow through said at least said one ofsaid first and second pumps responsively to said ultrafiltration data.

According to third embodiments, the disclosed subject matter includes amedical treatment system with a controller and control valve actuatorsand first and second pumps, the control valve actuators and pumps iscontrolled by the controller. The first pump is controlled to regulateflow toward a patient interface device and the second pump is controlledto regulate flow from the same patient interface device. The patientinterface device is a device that is separate from the claimed treatmentsystem that interfaces with a patient fluid compartment includes atleast one of a dialyzer, a hemofilter, a hemodiafilter, an ultrafilter,and a plasmapheresis device. The controller includes a processorprogrammed to regulate the speed of the first and second pumps toachieve a predefined net removal of fluid from the patient interfacedevice during a treatment interval. The processor is further programmedto control the control valve actuators to switch between a firstposition that configures a fluid circuit, when attached to the controlvalves, in a bypass configuration which defines a bypass flow path thatbypasses the patient interface device, and a second position whichdefines a flow path into and out of the patient interface device. Apressure transducer is connected to convey pressure signals to thecontroller, the pressure signals indicating pressure in the bypass flowpath. the controller is programmed to calculate and store flowcorrection data representing a correction to be applied to a rate offlow of the at least one of the first and second fluid managementelements responsively to the signal. The controller is furtherprogrammed to modify a flow rate of the at least one of the first andsecond fluid management elements responsively to the flow correctiondata.

The third embodiments can be modified to form additional thirdembodiments in which a diverted flow in the calibration configurationflows between the first and second fluid management elements through afluid accumulator connected to a pressure sensor that outputs thesignal. The third embodiments can be modified to form additional thirdembodiments in which the accumulator is configured such that pressureincreases as fluid fills the accumulator, whereby a difference in theflow rates of the first and second fluid management elements results inan increasing or decreasing pressure. The third embodiments can bemodified to form additional third embodiments in which the accumulatorhas a residual volume of fluid to permit the measurement of a pressurechange caused by a net removal or a net addition of fluid from or to theaccumulator. The third embodiments can be modified to form additionalthird embodiments in which the first fluid management element includes aperistaltic pump. The third embodiments can be modified to formadditional third embodiments in which the fluid circuit includes adisposable plastic tubing set and at least one control valve, thecontrol valve includes a tubing junction that interfaces with one ormore pinch clamps to form selectable flow paths, the pinch clamps ispermanent reusable elements that pinch respective portions of the tubingset. The third embodiments can be modified to form additional thirdembodiments in which a third fluid management element pumps fluid intothe patient interface device during a treatment, the third fluidmanagement element is coupled to a synchronization mechanism that causesthe first and third fluid management elements to pump equal amounts offluid per unit time during a treatment.

The third embodiments can be modified to form additional thirdembodiments in which a third fluid management element pumps fluid intothe patient interface device during a treatment, the third fluidmanagement element is coupled to a mechanical synchronization mechanismthat causes the first and third fluid management elements to move suchthat they pump equal amounts of fluid per unit time during a treatmentthrough the fluid circuit. The third embodiments can be modified to formadditional third embodiments in which a blood circuit interfaces withthe patient interface device and, through the latter, to the fluidcircuit. The third embodiments can be modified to form additional thirdembodiments in which the flow or pressure sensor is a flow sensor. Thethird embodiments can be modified to form additional third embodimentsin which a blood circuit interfaces with the patient interface deviceand, through the latter, to the fluid circuit and wherein a divertedflow in the calibration configuration flows through a flow path betweenthe first and second fluid management elements through a fluidaccumulator connected to a pressure sensor that outputs the signal,wherein a fluid circuit portion connected to the patient interfacedevice is separate from the flow path. The third embodiments can bemodified to form additional third embodiments in which the second fluidmanagement element is connected to a source of a medicament. The thirdembodiments can be modified to form additional third embodiments inwhich the controller is connected to a user interface and programmed toaccept and store ultrafiltration data representing a target netultrafiltration, wherein the controller is further programmed to controlflow through the at least the one of the first and second fluidmanagement elements responsively to the ultrafiltration data.

According to fourth embodiments, the disclosed subject matter includes amethod of regulating the balanced flow of fluids with in a system hasfirst and second fluid channels each with at least one respective pumpfor each of the first and second fluid channels. The method includesusing a controller to control the rate of pumping of one or more of therespective pumps to establish flows in the first and second channels ofequal volume flow rate based on calibration data stored in thecontroller. The first and second channels connect to a fluid handlingdevice in which a ratio of flow rates of entering and leaving flows toand from the fluid handling device is maintained by the controller. Themethod further includes using the controller, temporarily establishing aflow from the first channel to the second channel through a test flowbranch with a pressure sensor and receiving a signal of a test branchpressure in the test branch at the controller. The method furtherincludes, in response to the test branch pressure signal, using thecontroller, adjusting the calibration data. thereafter, using thecontroller, adjusting one or more of the respective pumps according tothe calibration data adjusted by the adjusting.

The fourth embodiments can be modified to form additional fourthembodiments in which the controller receives a local pressure upstreamand/or downstream of at least one of the respective pumps, the adjustingbeing responsive to both the test branch pressure signal and the localpressure signal. The fourth embodiments can be modified to formadditional fourth embodiments in which the receiving a local pressureincludes receiving local pressures upstream and downstream of the atleast one of the respective pumps. The fourth embodiments can bemodified to form additional fourth embodiments in which the controllercontrols a valve that selectively permits flow through the test flowbranch and the controller automatically selects a time of thetemporarily establishing. The fourth embodiments can be modified to formadditional fourth embodiments in which the controller controls a valvethat selectively permits flow through the test flow branch and thecontroller automatically selects multiple instances of the temporarilyestablishing. The fourth embodiments can be modified to form additionalfourth embodiments in which the fluid handling device is a bloodtreatment device. The fourth embodiments can be modified to formadditional fourth embodiments in which the blood treatment device is adialyzer or a hemofilter and replacement fluid source. The fourthembodiments can be modified to form additional fourth embodiments inwhich the respective pumps are peristaltic pumps. The fourth embodimentscan be modified to form additional fourth embodiments in which therespective pumps are of a type that produce pressure pulses at regularintervals during pumping, the respective pumps is selected such that thepressure pulses of pumps flowing into and out of the test flow branchdiffer by at least a factor of two at pumping rates that occur timesother than at times of the temporarily establishing. The fourthembodiments can be modified to form additional fourth embodiments inwhich the respective pumps are peristaltic pumps and pumping tubesegments of no one of the respective pumps responsible for the enteringflow has an inner diameter the same as a pumping tube segment innerdiameter of a one of the respective pumps responsible for the leavingflow. The fourth embodiments can be modified to form additional fourthembodiments in which the respective pumps are peristaltic pumps and thenumber of rollers for no one of the respective pumps responsible for theentering flow is the same as the number of rollers of a one of therespective pumps responsible for the leaving flow. The fourthembodiments can be modified to form additional fourth embodiments inwhich the controller stores data representing operating conditions thatcoincide with respective pumps are of a type that produce pressurepulses at regular intervals during pumping, the respective pumps isselected such that the pressure pulses of pumps flowing into and out ofthe test flow branch differ by at least a factor of two at pumping ratesthat occur times other than at times of the temporarily establishing.

According to fifth embodiments, the disclosed subject matter includes amethod of maintaining a predefined ratio of flow rates in first andsecond channels with connecting the first and second channelstemporarily to create a continuous flow between them. The methodincludes measuring a static pressure of a channel carrying thecontinuous flow temporarily generated in the connecting. The methodfurther includes adjusting calibration data of one or more respectivepumps that generate at least one of the second flows responsively to aresult of the measuring.

The fifth embodiments can be modified to form additional fifthembodiments in which the connecting, measuring, and adjusting are doneautomatically by a programmable controller, the method furthercomprising adjusting a speed of the one or more respective pumps inresponse to the calibration data. The fifth embodiments can be modifiedto form additional fifth embodiments including limiting low frequencypressure fluctuations in the continuous flow. The fifth embodiments canbe modified to form additional fifth embodiments in which the limitingincludes selecting the one or more respective pumps whose pulsationfrequencies at a rate of the continuous flow produce beats due tosuperposition of the pulsations that are either multiple times shorterthan, or multiple times longer than a period of the measuring, themeasuring includes sampling the static pressure multiple times over theperiod of the measuring. The fifth embodiments can be modified to formadditional fifth embodiments in which the limiting includes adjustingthe one or more respective pumps to a rate of the continuous flow thatproduces beats due to superposition of the pulsations thereof that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring, the one ormore respective pumps has different ratios of flow rate to pulsationfrequencies. The fifth embodiments can be modified to form additionalfifth embodiments in which the one or more respective pumps havedifferent ratios as a result of has differences in one or a combinationof tubing inner diameter or number of rollers of a peristaltic pumprotor. The fifth embodiments can be modified to form additional fifthembodiments in which one or both of the first and second channelsincludes at least two fluid lines. The fifth embodiments can be modifiedto form additional fifth embodiments in which the connecting, measuring,and adjusting are done automatically by a programmable controller, themethod further comprising adjusting a speed of the one or morerespective pumps in response to the calibration data. The fifthembodiments can be modified to form additional fifth embodiments furtherincluding limiting low frequency pressure fluctuations in the continuousflow. The fifth embodiments can be modified to form additional fifthembodiments in which the limiting includes selecting the one or morerespective pumps whose pulsation frequencies at a rate of the continuousflow produce beats due to superposition of the pulsations that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring. The fifthembodiments can be modified to form additional fifth embodiments inwhich the limiting includes adjusting the one or more respective pumpsto a rate of the continuous flow that produces beats due tosuperposition of the pulsations thereof that are either multiple timesshorter than, or multiple times longer than a period of the measuring,the measuring includes sampling the static pressure multiple times overthe period of the measuring, the one or more respective pumps hasdifferent ratios of flow rate to pulsation frequencies. The fifthembodiments can be modified to form additional fifth embodiments inwhich the one or more respective pumps have different ratios as a resultof has differences in one or a combination of tubing inner diameter,suction side head pressure, or number of rollers of a respectiveperistaltic pump rotor. The fifth embodiments can be modified to formadditional fifth embodiments in which the first and second flow channelsare, at times other than the measuring, connected by a controller to amedical treatment device for the supply and withdrawal of treatmentfluid. The fifth embodiments can be modified to form additional fifthembodiments in which the medical treatment device includes a renalreplacement therapy system and the treatment fluid includes dialysate orelectrolyte.

According to sixth embodiments, the disclosed subject matter includes asystem for regulating the balanced flow of fluids with first and secondfluid channels each with at least one respective pump for each of thefirst and second fluid channels. A controller is connected to therespective pumps to control the rate of pumping of one or more of therespective pumps. The controller is connected to one or more valves topermit it to establish flows in the first and second channels of equalvolume flow rate responsively to calibration data stored in thecontroller. The first and second channels connect to a fluid handlingdevice in which a ratio of flow rates of entering and leaving flows toand from the fluid handling device is maintained by the controller. thecontroller, at selected times, temporarily establishing a flow from thefirst channel to the second channel through a test flow branch,connected through the one or more valves, with a pressure sensor andsampling a signal of a test branch pressure in the test branch at thecontroller. In response to the samples, the controller adjusts thecalibration data stored in the controller. the controller, using theadjusted calibration data stored in the controller to adjust the one ormore of the respective pumps.

The sixth embodiments can be modified to form additional sixthembodiments in which the controller is connected to receive a localpressure upstream and/or downstream of at least one of the respectivepumps, the adjusting is responsive to both the test branch pressuresignal and the local pressure signal. The sixth embodiments can bemodified to form additional sixth embodiments in which the receivedlocal pressure includes local pressures upstream and downstream of theat least one of the respective pumps. The sixth embodiments can bemodified to form additional sixth embodiments in which the controllercontrols a valve that selectively permits flow through the test flowbranch and the controller automatically selects a time of establishingthe continuous flow and performing the sampling. The sixth embodimentscan be modified to form additional sixth embodiments in which thecontroller controls a valve that selectively permits flow through thetest flow branch and the controller automatically iterativelyestablishes the continuous flow and the performance of the sampling. Thesixth embodiments can be modified to form additional sixth embodimentsin which the fluid handling device is a blood treatment device. Thesixth embodiments can be modified to form additional sixth embodimentsin which the blood treatment device is a dialyzer or a hemofilter andreplacement fluid source. The sixth embodiments can be modified to formadditional sixth embodiments in which the respective pumps areperistaltic pumps. The sixth embodiments can be modified to formadditional sixth embodiments in which the respective pumps are of a typethat produce pressure pulses at regular intervals during pumping, therespective pumps is selected such that the pressure pulses of pumpsflowing into and out of the test flow branch differ by at least a factorof two at pumping rates that occur times other than at times of thetemporarily establishing. The sixth embodiments can be modified to formadditional sixth embodiments in which the respective pumps areperistaltic pumps and pumping tube segments of no one of the respectivepumps responsible for the entering flow has an inner diameter the sameas a pumping tube segment inner diameter of a one of the respectivepumps responsible for the leaving flow. The sixth embodiments can bemodified to form additional sixth embodiments in which the respectivepumps are peristaltic pumps and the number of rollers for no one of therespective pumps responsible for the entering flow is the same as thenumber of rollers of a one of the respective pumps responsible for theleaving flow. The sixth embodiments can be modified to form additionalsixth embodiments in which the controller stores data representingoperating conditions that coincide with respective pumps are of a typethat produce pressure pulses at regular intervals during pumping, therespective pumps is selected such that the pressure pulses of pumpsflowing into and out of the test flow branch differ by at least a factorof two at pumping rates that occur times other than at times of thetemporarily establishing.

According to seventh embodiments, the disclosed subject matter includesa method for maintaining a predefined ratio of flow rates in first andsecond channels. The method includes connecting the first and secondchannels temporarily to create a continuous flow between them. Themethod further includes measuring a static pressure of a channelcarrying the continuous flow temporarily generated in the connecting.adjusting calibration data of one or more respective pumps that generateat least one of the second flows responsively to a result of themeasuring.

The seventh embodiments can be modified to form additional seventhembodiments in which the connecting, measuring, and adjusting are doneautomatically by a programmable controller, the system furthercomprising adjusting a speed of the one or more respective pumps inresponse to the calibration data. The seventh embodiments can bemodified to form additional seventh embodiments in which the first andsecond flow channels and/or the test branch and/or the one at least onerespective pump are configured to limit low frequency pressurefluctuations in the continuous flow due to the superposition of pressurepulses of the respective pumps that form beats. The seventh embodimentscan be modified to form additional seventh embodiments in which the oneor more respective pumps have pulsation frequencies at a rate of thecontinuous flow that produces beats due to superposition of thepulsations that are either multiple times shorter than, or multipletimes longer than a period of the measuring, the measuring includessampling the static pressure multiple times over the period of themeasuring. The seventh embodiments can be modified to form additionalseventh embodiments in which the one or more respective pumps arecontrolled to a rate of the continuous flow that produces beats due tosuperposition of the pulsations thereof that are either multiple timesshorter than, or multiple times longer than a period of the measuring,the measuring includes sampling the static pressure multiple times overthe period of the measuring, the one or more respective pumps hasdifferent ratios of flow rate to pulsation frequencies. The seventhembodiments can be modified to form additional seventh embodiments inwhich the one or more respective pumps have different ratios as a resultof has differences in one or a combination of tubing inner diameter ornumber of rollers of a peristaltic pump rotor. The seventh embodimentscan be modified to form additional seventh embodiments in which one orboth of the first and second channels includes at least two fluid lines.The seventh embodiments can be modified to form additional seventhembodiments in which the connecting, measuring, and adjusting are doneautomatically by a programmable controller, the system furthercomprising adjusting a speed of the one or more respective pumps inresponse to the calibration data. The seventh embodiments can bemodified to form additional seventh embodiments in which the first andsecond flow channels and/or the test branch and/or the one at least onerespective pump are configured to limit low frequency pressurefluctuations in the continuous flow due to the superposition of pressurepulses of the respective pumps that form beats. The seventh embodimentscan be modified to form additional seventh embodiments in which the oneor more respective pumps have pulsation frequencies at a rate of thecontinuous flow that produces beats due to superposition of thepulsations that are either multiple times shorter than, or multipletimes longer than a period of the measuring, the measuring includessampling the static pressure multiple times over the period of themeasuring. The seventh embodiments can be modified to form additionalseventh embodiments in which the one or more respective pumps arecontrolled to a rate of the continuous flow that produces beats due tosuperposition of the pulsations thereof that are either multiple timesshorter than, or multiple times longer than a period of the measuring,the measuring includes sampling the static pressure multiple times overthe period of the measuring, the one or more respective pumps hasdifferent ratios of flow rate to pulsation frequencies. The seventhembodiments can be modified to form additional seventh embodiments inwhich the one or more respective pumps have different ratios as a resultof has differences in one or a combination of tubing inner diameter ornumber of rollers of a peristaltic pump rotor. The seventh embodimentscan be modified to form additional seventh embodiments in which thefirst and second flow channels are, at times other than at times thatthe continuous flow is established by the controller, connected by thecontroller to a medical treatment device for the supply and withdrawalof treatment fluid. The seventh embodiments can be modified to formadditional seventh embodiments in which the medical treatment deviceincludes a renal replacement therapy system and the treatment fluidincludes dialysate or electrolyte.

According to eighth embodiments, the disclosed subject matter includes ablood treatment device with one or more inflow pumps and one or moreoutflow pumps that are configured to be interoperable with a replaceabletubing set that engages with the one or more inflow and outflow pumps toestablish flows into and out of a treatment device and/or a patientaccess connectable to the tubing set. The flows into and out of thetreatment device are established in inflow and outflow channel portionsof the tubing set, respectively. One or more valve actuatorsinteroperable with the tubing set to divert flow through a branchchannel thereof, the branch channel fluidly coupling the inflow andoutflow channel portions of the tubing set that are in engagement withthe one or more inflow and one or more outflow pumps. a programmablecontroller connected to control speeds of the one or more inflow and oneor more outflow pumps. The programmable controller is connected tocontrol the valve actuators. the programmable controller has a pressureterminal that receives pressure signals from a pressure sensor inengagement with the branch channel of a connected tubing set. Theprogrammable controller has a data storage storing calibration data thatallows the controller to establish predefined flow rates in the one ormore inflow and one or more outflow pumps. The data storage furtherstores instructions which, when executed, cause the controller tooperate the one or more inflow and one or more outflow pumps to performa blood treatment using the calibration data to control flows in theinflow and outflow channels and automatically and temporarily generate aflow in the branch channel and store pressure samples in the datastorage over a sampling period. The controller further corrects at leastportions of the calibration data in response to the samples.

The eighth embodiments can be modified to form additional eighthembodiments in which the branch channel has an accumulator chamber witha diaphragm on a side thereof, forming a pressure pod, which transmitspressurized air to the pressure sensor, the pressure sensor includes apressure transducer. The eighth embodiments can be modified to formadditional eighth embodiments in which the one or more inflow andoutflow pumps are peristaltic pumps. The eighth embodiments can bemodified to form additional eighth embodiments in which inflow ones ofthe one or more inflow and outflow pumps generate different pressurepulse frequencies for a given flow rate than outflow ones of the one ormore inflow and outflow pumps for the given flow rate. The eighthembodiments can be modified to form additional eighth embodiments inwhich inflow ones of the one or more inflow and outflow pumps generatedifferent pressure pulse frequencies for a given flow rate than outflowones of the one or more inflow and outflow pumps for the given flow rateas a result of differences in the inner diameters of respective pumpingportions of the tubing set. The eighth embodiments can be modified toform additional eighth embodiments in which inflow ones of the one ormore inflow and outflow pumps generate different pressure pulsefrequencies for a given flow rate than outflow ones of the one or moreinflow and outflow pumps for the given flow rate as a result ofdifferences in the number of rollers among the one or more inflow andoutflow pumps. The eighth embodiments can be modified to form additionaleighth embodiments in which the controller is programmed to modify atleast one parameter of pumping by the one or more inflow and outflowpumps such that beats resulting from a superposition of the pulses inthe branch channel are either multiple times shorter than, or multipletimes longer than a period of the measuring. The eighth embodiments canbe modified to form additional eighth embodiments in which the at leastone parameter includes a controlling a net flow rate through the branchchannel such that predefined ranges of the net flow are avoided.

The eighth embodiments can be modified to form additional eighthembodiments in which the at least one parameter includes a suction headof at least one of the one or more inflow and outflow pumps. The eighthembodiments can be modified to form additional eighth embodiments inwhich the at least one parameter includes an inlet-outlet pressuredifferential of at least one of the one or more inflow and outflowpumps. The eighth embodiments can be modified to form additional eighthembodiments in which the at least one parameter includes a volumetricefficiency of at least one of the one or more inflow and outflow pumps.The eighth embodiments can be modified to form additional eighthembodiments in which the at least one parameter includes a phase angleof at least one of the one or more inflow and outflow pumps relative toat least another of the one or more inflow and outflow pumps. The eighthembodiments can be modified to form additional eighth embodiments inwhich the at least one parameter includes a flow restriction positionedto restrict flow upstream and/or downstream of the one or more inflowand outflow pumps.

According to ninth embodiments, the disclosed subject matter includes amethod of regulating the balanced flow of fluids with at productiontimes, in a system has first and second fluid channels each with atleast one respective pump for each of the first and second fluidchannels. The method includes using a controller to control the rate ofpumping of one or more of the respective pumps to establish flows in thefirst and second channels with volume flow rates of a predefined ratiobased on calibration data stored in the controller. The first and secondchannels connect to a fluid handling device. The method includes, attest times, using the controller, temporarily establishing a flow fromthe first channel to the second channel through a test flow branch witha pressure sensor and receiving, and storing static pressure datarepresenting, a test branch pressure in the test branch at thecontroller. The method includes adjusting a flow restriction in thefirst channel, the second channel, or the test branch to make the inletand/or outlet pressure of one or more of the at least one respectivepumps equal to a predefined pressure. The method includes, in responseto the static pressure data, using the controller, revising thecalibration data. thereafter, using the controller, adjusting one ormore of the respective pumps according to the calibration data adjustedby the adjusting.

The ninth embodiments can be modified to form additional ninthembodiments including, prior to the test times, measuring a pressureinto or out of one of the respective pumps and storing a targetpressure, the predefined pressure is responsive to the target pressure.The ninth embodiments can be modified to form additional ninthembodiments including, at test times, adjusting a phase angle betweentwo of the respective pumps such that sampling bias in the staticpressure data is reduced. The ninth embodiments can be modified to formadditional ninth embodiments including, at test times, adjusting a phaseangle between two of the respective pumps such that sampling bias in thestatic pressure data does not exceed a wavelength of that of a pressurepulsation generated by either of the two of the respective pumps. Theninth embodiments can be modified to form additional ninth embodimentsin which wherein the adjusting is effective to make any beats due tofluctuations caused by beat interference between pressure pulsesgenerated by the respective pumps to be at a frequency that is multipletimes higher than an inverse of the an interval of the test times. Theninth embodiments can be modified to form additional ninth embodimentsin which the revising is in response to a moving average of the staticpressure data generated using a non-rectangular averaging window. Theninth embodiments can be modified to form additional ninth embodimentsin which the sampling frequency of the static pressure data is at leastten times a highest frequency of pressure pulses resulting from eitherof the one or more respective pumps. The ninth embodiments can bemodified to form additional ninth embodiments in which the controllerreceives a local pressure upstream and/or downstream of at least one ofthe respective pumps, the adjusting is responsive to both the testbranch pressure signal and the local pressure signal. The ninthembodiments can be modified to form additional ninth embodiments inwhich the receiving a local pressure includes receiving local pressuresupstream and downstream of the at least one of the respective pumps. Theninth embodiments can be modified to form additional ninth embodimentsin which the controller controls a valve that selectively permits flowthrough the test flow branch and the controller automatically selects atime of the temporarily establishing. The ninth embodiments can bemodified to form additional ninth embodiments in which the controllercontrols a valve that selectively permits flow through the test flowbranch and the controller automatically selects multiple instances ofthe temporarily establishing. The ninth embodiments can be modified toform additional ninth embodiments in which the fluid handling device isa blood treatment device. The ninth embodiments can be modified to formadditional ninth embodiments in which the blood treatment device is adialyzer or a hemofilter and replacement fluid source. The ninthembodiments can be modified to form additional ninth embodiments inwhich the respective pumps are peristaltic pumps. The ninth embodimentscan be modified to form additional ninth embodiments in which therespective pumps are of a type that produce pressure pulses at regularintervals during pumping, the respective pumps is selected such that thepressure pulses of pumps flowing into and out of the test flow branchdiffer by at least a factor of two at pumping rates that occur timesother than at times of the temporarily establishing. The ninthembodiments can be modified to form additional ninth embodiments inwhich the respective pumps are peristaltic pumps and pumping tubesegments of no one of the respective pumps responsible for the enteringflow has an inner diameter the same as a pumping tube segment innerdiameter of a one of the respective pumps responsible for the leavingflow. The ninth embodiments can be modified to form additional ninthembodiments in which the respective pumps are peristaltic pumps and thenumber of rollers for no one of the respective pumps responsible for theentering flow is the same as the number of rollers of a one of therespective pumps responsible for the leaving flow. The ninth embodimentscan be modified to form additional ninth embodiments in which thecontroller stores data representing operating conditions that coincidewith respective pumps are of a type that produce pressure pulses atregular intervals during pumping, the respective pumps is selected suchthat the pressure pulses of pumps flowing into and out of the test flowbranch differ by at least a factor of two at pumping rates that occurtimes other than at times of the temporarily establishing.

According to tenth embodiments, the disclosed subject matter includes amethod of maintaining a predefined ratio of flow rates in first andsecond channels with connecting the first and second channelstemporarily to create a continuous flow between them. The methodincludes measuring a static pressure of a channel carrying thecontinuous flow temporarily generated in the connecting and adjustingcalibration data of one or more respective pumps that generate at leastone of the second flows responsively to a result of the measuring.

The tenth embodiments can be modified to form additional tenthembodiments in which the connecting, measuring, and adjusting are doneautomatically by a programmable controller, the method furthercomprising adjusting a speed of the one or more respective pumps inresponse to the calibration data. The tenth embodiments can be modifiedto form additional tenth embodiments that include limiting low frequencypressure fluctuations in the continuous flow. The tenth embodiments canbe modified to form additional tenth embodiments in which the limitingincludes selecting the one or more respective pumps whose pulsationfrequencies at a rate of the continuous flow produce beats due tosuperposition of the pulsations that are either multiple times shorterthan, or multiple times longer than a period of the measuring, themeasuring includes sampling the static pressure multiple times over theperiod of the measuring. The tenth embodiments can be modified to formadditional tenth embodiments in which the limiting includes adjustingthe one or more respective pumps to a rate of the continuous flow thatproduces beats due to superposition of the pulsations thereof that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring, the one ormore respective pumps has different ratios of flow rate to pulsationfrequencies. The tenth embodiments can be modified to form additionaltenth embodiments in which the one or more respective pumps havedifferent ratios as a result of has differences in one or a combinationof tubing inner diameter or number of rollers of a peristaltic pumprotor. The tenth embodiments can be modified to form additional tenthembodiments in which one or both of the first and second channelsincludes at least two fluid lines. The tenth embodiments can be modifiedto form additional tenth embodiments in which the connecting, measuring,and adjusting are done automatically by a programmable controller, themethod further comprising adjusting a speed of the one or morerespective pumps in response to the calibration data. The tenthembodiments can be modified to form additional tenth embodiments thatinclude limiting low frequency pressure fluctuations in the continuousflow. The tenth embodiments can be modified to form additional tenthembodiments in which the limiting includes selecting the one or morerespective pumps whose pulsation frequencies at a rate of the continuousflow produce beats due to superposition of the pulsations that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring. The tenthembodiments can be modified to form additional tenth embodiments inwhich the limiting includes adjusting the one or more respective pumpsto a rate of the continuous flow that produces beats due tosuperposition of the pulsations thereof that are either multiple timesshorter than, or multiple times longer than a period of the measuring,the measuring includes sampling the static pressure multiple times overthe period of the measuring, the one or more respective pumps hasdifferent ratios of flow rate to pulsation frequencies. The tenthembodiments can be modified to form additional tenth embodiments inwhich the one or more respective pumps have different ratios as a resultof has differences in one or a combination of tubing inner diameter,suction side head pressure, or number of rollers of a respectiveperistaltic pump rotor. The tenth embodiments can be modified to formadditional tenth embodiments in which the first and second flow channelsare, at times other than the measuring, connected by a controller to amedical treatment device for the supply and withdrawal of treatmentfluid. The tenth embodiments can be modified to form additional tenthembodiments in which the medical treatment device includes a renalreplacement therapy system and the treatment fluid includes dialysate orelectrolyte.

According to eleventh embodiments, the disclosed subject matter includesa system for regulating balanced flow of fluids with first and secondfluid channels connectable to a fluid handling device, each with atleast one respective pump for each of the first and second fluidchannels, a controller connected to the respective pumps to control therate of pumping of one or more of the respective pumps, the controlleris connected to one or more valves to permit it to establish flows inthe first and second channels. A ratio of flow rates of entering andleaving flows to and from the fluid handling device is controlled by thecontroller to effect a predefined net transfer of fluid to or from thefluid handling device responsively to calibration data accessible to thecontroller. The controller, at selected times, temporarily establishes abypass flow directly from the first channel to the second channel,thereby bypassing connectors to the fluid handling device, through atest flow branch by defining selected flow paths through the one or morevalves. a pressure sensor device in the test flow branch, the controllersampling a signal of the bypass flow pressure in the test branch and inresponse to the samples, the controller adjusting the calibration data.The controller, uses the adjusted calibration data stored in thecontroller to adjust the one or more of the respective pumps in order toeffect the predefined net transfer of fluid to or from the fluidhandling device.

The eleventh embodiments can be modified to form additional eleventhembodiments in which the controller is connected to receive a localpressure upstream and/or downstream of at least one of the respectivepumps, the adjusting is responsive to both the test branch pressuresignal and the local pressure signal. The eleventh embodiments can bemodified to form additional eleventh embodiments in which the receivedlocal pressure includes local pressures upstream and/or downstream ofthe at least one of the respective pumps. The eleventh embodiments canbe modified to form additional eleventh embodiments in which thecontroller controls a valve that selectively permits flow through thetest flow branch and the controller automatically selects a time ofestablishing the continuous flow and performing the sampling. Theeleventh embodiments can be modified to form additional eleventhembodiments in which the controller controls a valve that selectivelypermits flow through the test flow branch and the controllerautomatically iteratively establishes the continuous flow and theperformance of the sampling. The eleventh embodiments can be modified toform additional eleventh embodiments in which the fluid handling deviceis a blood treatment device. The eleventh embodiments can be modified toform additional eleventh embodiments in which the blood treatment deviceis a dialyzer or a hemofilter and replacement fluid source. The eleventhembodiments can be modified to form additional eleventh embodiments inwhich the respective pumps are peristaltic pumps. The eleventhembodiments can be modified to form additional eleventh embodiments inwhich the respective pumps are of a type that produce pressure pulses atregular intervals during pumping, the respective pumps is selected suchthat the pressure pulses of pumps flowing into and out of the test flowbranch differ by at least a factor of two at pumping rates that occurtimes other than at times of the temporarily establishing. The eleventhembodiments can be modified to form additional eleventh embodiments inwhich the respective pumps are peristaltic pumps and pumping tubesegments of no one of the respective pumps responsible for the enteringflow has an inner diameter the same as a pumping tube segment innerdiameter of a one of the respective pumps responsible for the leavingflow. The eleventh embodiments can be modified to form additionaleleventh embodiments in which the respective pumps are peristaltic pumpsand the number of rollers for no one of the respective pumps responsiblefor the entering flow is the same as the number of rollers of a one ofthe respective pumps responsible for the leaving flow. The eleventhembodiments can be modified to form additional eleventh embodiments inwhich the controller stores data representing operating conditions thatcoincide with respective pumps are of a type that produce pressurepulses at regular intervals during pumping, the respective pumps isselected such that the pressure pulses of pumps flowing into and out ofthe test flow branch differ by at least a factor of two at pumping ratesthat occur times other than at times of the temporarily establishing.

According to twelfth embodiments, the disclosed subject matter includesa method for maintaining a predefined ratio of flow rates in first andsecond channels with connecting the first and second channelstemporarily to create a continuous flow between them. The methodincludes measuring a static pressure of a channel carrying thecontinuous flow temporarily generated in the connecting. The methodincludes adjusting calibration data of one or more respective pumps thatgenerate at least one of the second flows responsively to a result ofthe measuring.

The twelfth embodiments can be modified to form additional twelfthembodiments in which the connecting, measuring, and adjusting are doneautomatically by a programmable controller, the system furthercomprising adjusting a speed of the one or more respective pumps inresponse to the calibration data.

The twelfth embodiments can be modified to form additional twelfthembodiments in which the first and second flow channels and/or the testbranch and/or the one at least one respective pump are configured tolimit low frequency pressure fluctuations in the continuous flow due tothe superposition of pressure pulses of the respective pumps that formbeats. The twelfth embodiments can be modified to form additionaltwelfth embodiments in which the one or more respective pumps havepulsation frequencies at a rate of the continuous flow that producesbeats due to superposition of the pulsations that are either multipletimes shorter than, or multiple times longer than a period of themeasuring, the measuring includes sampling the static pressure multipletimes over the period of the measuring. The twelfth embodiments can bemodified to form additional twelfth embodiments in which the one or morerespective pumps are controlled to a rate of the continuous flow thatproduces beats due to superposition of the pulsations thereof that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring, the one ormore respective pumps has different ratios of flow rate to pulsationfrequencies.

The twelfth embodiments can be modified to form additional twelfthembodiments in which the one or more respective pumps have differentratios as a result of has differences in one or a combination of tubinginner diameter or number of rollers of a peristaltic pump rotor. Thetwelfth embodiments can be modified to form additional twelfthembodiments in which one or both of the first and second channelsincludes at least two fluid lines. The twelfth embodiments can bemodified to form additional twelfth embodiments in which the connecting,measuring, and adjusting are done automatically by a programmablecontroller, the system further comprising adjusting a speed of the oneor more respective pumps in response to the calibration data. Thetwelfth embodiments can be modified to form additional twelfthembodiments in which the first and second flow channels and/or the testbranch and/or the one at least one respective pump are configured tolimit low frequency pressure fluctuations in the continuous flow due tothe superposition of pressure pulses of the respective pumps that formbeats. The twelfth embodiments can be modified to form additionaltwelfth embodiments in which the one or more respective pumps havepulsation frequencies at a rate of the continuous flow that producesbeats due to superposition of the pulsations that are either multipletimes shorter than, or multiple times longer than a period of themeasuring, the measuring includes sampling the static pressure multipletimes over the period of the measuring. The twelfth embodiments can bemodified to form additional twelfth embodiments in which the one or morerespective pumps are controlled to a rate of the continuous flow thatproduces beats due to superposition of the pulsations thereof that areeither multiple times shorter than, or multiple times longer than aperiod of the measuring, the measuring includes sampling the staticpressure multiple times over the period of the measuring, the one ormore respective pumps has different ratios of flow rate to pulsationfrequencies. The twelfth embodiments can be modified to form additionaltwelfth embodiments in which the one or more respective pumps havedifferent ratios as a result of has differences in one or a combinationof tubing inner diameter or number of rollers of a peristaltic pumprotor. The twelfth embodiments can be modified to form additionaltwelfth embodiments in which the first and second flow channels are, attimes other than at times that the continuous flow is established by thecontroller, connected. The twelfth embodiments can be modified to formadditional twelfth embodiments in which the medical treatment deviceincludes a renal replacement therapy system and the treatment fluidincludes dialysate or electrolyte.

According to thirteenth embodiments, the disclosed subject matterincludes a blood treatment device with one or more inflow pumps and oneor more outflow pumps that are configured to be interoperable with areplaceable tubing set that engages with the one or more inflow andoutflow pumps to establish flows into and out of a treatment deviceand/or a patient access connectable to the tubing set, the flows intoand out of the treatment device is established in inflow and outflowchannel portions of the tubing set, respectively. One or more valveactuators are interoperable with the tubing set to divert flow through abranch channel thereof, the branch channel fluidly coupling the inflowand outflow channel portions of the tubing set that are in engagementwith the one or more inflow and one or more outflow pumps. Aprogrammable controller connects to control speeds of the one or moreinflow and one or more outflow pumps. The programmable controller isconnected to control the valve actuators. the programmable controllerhas a pressure terminal that receives pressure signals from a pressuresensor in engagement with the branch channel of a connected tubing set.the programmable controller has a data storage storing calibration datathat allows the controller to establish predefined flow rates in the oneor more inflow and one or more outflow pumps, the data storage furtherstoring instructions which when executed, cause the controller tooperate the one or more inflow and one or more outflow pumps to performa blood treatment using the calibration data to control flows in theinflow and outflow channels, automatically and temporarily generate aflow in the branch channel and store pressure samples in the datastorage over a sampling period, and correct at least portions of thecalibration data in response to the samples.

The thirteenth embodiments can be modified to form additional thirteenthembodiments in which the branch channel has an accumulator chamber witha diaphragm on a side thereof, forming a pressure pod, which transmitspressurized air to the pressure sensor, the pressure sensor includes apressure transducer. The thirteenth embodiments can be modified to formadditional thirteenth embodiments in which the one or more inflow andoutflow pumps are peristaltic pumps. The thirteenth embodiments can bemodified to form additional thirteenth embodiments in which inflow onesof the one or more inflow and outflow pumps generate different pressurepulse frequencies for a given flow rate than outflow ones of the one ormore inflow and outflow pumps for the given flow rate. The thirteenthembodiments can be modified to form additional thirteenth embodiments inwhich inflow ones of the one or more inflow and outflow pumps generatedifferent pressure pulse frequencies for a given flow rate than outflowones of the one or more inflow and outflow pumps for the given flow rateas a result of differences in the inner diameters of respective pumpingportions of the tubing set. The thirteenth embodiments can be modifiedto form additional thirteenth embodiments in which inflow ones of theone or more inflow and outflow pumps generate different pressure pulsefrequencies for a given flow rate than outflow ones of the one or moreinflow and outflow pumps for the given flow rate as a result ofdifferences in the number of rollers among the one or more inflow andoutflow pumps. The thirteenth embodiments can be modified to formadditional thirteenth embodiments in which the controller is programmedto modify at least one parameter of pumping by the one or more inflowand outflow pumps such that beats resulting from a superposition of thepulses in the branch channel are either multiple times shorter than, ormultiple times longer than a period of the measuring. The thirteenthembodiments can be modified to form additional thirteenth embodiments inwhich the at least one parameter includes a controlling a net flow ratethrough the branch channel such that predefined ranges of the net floware avoided. The thirteenth embodiments can be modified to formadditional thirteenth embodiments in which the at least one parameterincludes a suction head of at least one of the one or more inflow andoutflow pumps. The thirteenth embodiments can be modified to formadditional thirteenth embodiments in which the at least one parameterincludes an inlet-outlet pressure differential of at least one of theone or more inflow and outflow pumps. The thirteenth embodiments can bemodified to form additional thirteenth embodiments in which the at leastone parameter includes a volumetric efficiency of at least one of theone or more inflow and outflow pumps. The thirteenth embodiments can bemodified to form additional thirteenth embodiments in which the at leastone parameter includes a phase angle of at least one of the one or moreinflow and outflow pumps relative to at least another of the one or moreinflow and outflow pumps. The thirteenth embodiments can be modified toform additional thirteenth embodiments in which the at least oneparameter includes a flow restriction positioned to restrict flowupstream and/or downstream of the one or more inflow and outflow pumps.

According to fourteenth embodiments, the disclosed subject matterincludes a flow balancing system for a blood treatment device with oneor more inflow pumps and one or more outflow pumps positioned to engagea replaceable fluid circuit to pump fluid into and out of a treatmentdevice, respectively. At least one adjustable flow-restricting actuatorgenerates a flow restriction of a selected magnitude in at least oneportion of the replaceable fluid circuit, each located at an inlet of arespective one of the one or more inflow and outflow pumps so as togenerate a selectable suction head during pumping. Valve actuatorscontrol valve portions of the replaceable fluid circuit. a controllerconnected to the one or more inflow and outflow pumps to control speedsthereof, connected to control the valve actuators, and connected tocontrol the at least one adjustable flow-restricting actuator. Thecontroller has a data store storing a model that predicts dataindicative of a flow rate based on at least one of pump speed and inletand/or outlet pressure of each of the one or more inflow and outflowpumps. The replaceable fluid circuit has inflow, outflow, and bridgechannels, the inflow and outflow channels connecting to the treatmentdevice, the inflow and outflow channels is connected to the bridgechannel such that they can be bridged by the valve actuators to causeflow in the inflow channel to bypass the treatment device flowing fromthe inflow channel through the branch channel to the outlet channel. Oneor more pressure sensors are interoperable with the bridge channel todetect pressure at a respective one or more points therealong. Thecontroller is programmed to, generate a test command and in responsethereto, perform a calibration procedure during which it bridges theinflow and outflow channels through the branch channel and calculate adifference in flow rates between the one or more inflow and the one oroutflow pumps through the branch channel and, responsively thereto,calculates adjustments to the model. the controller is programmed tocontrol the one or more inflow and outflow pumps responsively to themodel.

The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the difference in flow rates between the one ormore inflow and the one or outflow pumps through the branch channel iscalculated from pressure signals indicating a pressure drop in thebranch channel. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the difference in flow ratesbetween the one or more inflow and the one or outflow pumps through thebranch channel is calculated from a single pressure signal indicating anet inflow or net outflow from the branch channel. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to generate the test command upon thedetection of a predefined operating time interval of one of the one ormore inflow and outflow pumps.

The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the controller is programmed to generate the testcommand upon the detection of a predefined number of rotations of theone or more inflow and outflow pumps. The fourteenth embodiments can bemodified to form additional fourteenth embodiments in which wherein thecontroller is programmed to generate the test command upon the detectionof a predefined net flow volume derived numerically from the number ofrotations of the one or more inflow and outflow pumps. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to adjust the at least one adjustableflow-restricting actuator to generate an inlet pressure of one of theone or more inflow and outflow pumps during the calibration operation.The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the controller is programmed to adjust the at leastone adjustable flow-restricting actuator to generate a first inletpressure at one of the one or more inflow and outflow pumps during thecalibration operation matching a second inlet pressure occurring duringa treatment operation. The fourteenth embodiments can be modified toform additional fourteenth embodiments in which the controller isprogrammed to adjust the at least one adjustable flow-restrictingactuator to generate multiple first inlet pressures at one of the one ormore inflow and outflow pumps during the calibration operation. Thefourteenth embodiments can be modified to form additional fourteenthembodiments in which the difference in flow rates between the one ormore inflow and the one or outflow pumps through the branch channel iscalculated from pressure signals indicating a pressure drop in thebranch channel. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the difference in flow ratesbetween the one or more inflow and the one or outflow pumps through thebranch channel is calculated from a single pressure signal indicating anet inflow or net outflow from the branch channel. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to generate the test command upon thedetection of a predefined operating time interval of one of the one ormore inflow and outflow pumps. The fourteenth embodiments can bemodified to form additional fourteenth embodiments in which thecontroller is programmed to generate the test command upon the detectionof a predefined number of rotations of the one or more inflow andoutflow pumps. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which wherein the controller isprogrammed to generate the test command upon the detection of apredefined net flow volume derived numerically from the number ofrotations of the one or more inflow and outflow pumps. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to adjust the at least one adjustableflow-restricting actuator to generate an inlet pressure of one of theone or more inflow and outflow pumps during the calibration operation.The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the difference in flow rates between the one ormore inflow and the one or outflow pumps through said branch channel iscalculated from pressure signals indicating a pressure drop in thebranch channel. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the controller is programmedto generate the test command upon the detection of a predefinedtemperature or temperature change of the replaceable fluid circuit. Thefourteenth embodiments can be modified to form additional fourteenthembodiments in which the controller is programmed to generate the testcommand upon the detection of a predefined pressure or pressure changeof at a location in the replaceable fluid circuit. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to control the valve actuators torecover fluid flowing through the branch channel for use in a treatment.The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the replaceable fluid circuit includes a storagevessel in communication with the outflow channel and the inflow channeland the controller is configured to direct fluid flowing through thebranch channel to the storage vessel and from the storage vessel to theinflow channel during a treatment, whereby fluid flowing in the branchchannel is recovered for use during treatment. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the model includes a lookup table representing a relationshipbetween inlet pressure, pump rotation speed, and flow. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the model includes a function representing a relationship betweeninlet pressure, pump rotation speed, and flow. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the model includes a data structure representing a relationshipbetween inlet pressure, pump rotation speed, and flow. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller calculates a difference in flow rates between theone or more inflow and the one or outflow pumps through the branchchannel responsively to a moving time-average pressure drop or pressure.The fourteenth embodiments can be modified to form additional fourteenthembodiments in which the controller calculates a difference in flowrates between the one or more inflow and the one or outflow pumpsthrough the branch channel responsively to a moving time-averagepressure drop or pressure generated from a non-rectangular averagingwindow. The fourteenth embodiments can be modified to form additionalfourteenth embodiments in which the controller calculates a differencein flow rates between the one or more inflow and the one or outflowpumps through the branch channel responsively to a moving time-averagepressure drop or pressure generated from a non-rectangular averagingwindow whose temporal length is greater than a wavelength of flow pulsescaused by the one or more inflow and outflow pumps flowing fluid throughthe branch channel. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the branch channel includesan accumulator. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the branch channel includesan accumulator with an internal volume in flow communication with thebranch channel, which internal volume size is selectable. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the branch channel includes an accumulator with an internal volumein flow communication with the branch channel, which internal volumesize is selectable under control of the controller. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to adjust the flow rate of the one ormore inflow and outflow pumps to generate multiple flow rates throughthe branch channel during the calibration operation. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the controller is programmed to adjust the at least one adjustableflow-restricting actuator to generate multiple first inlet pressures atone of the one or more inflow and outflow pumps during the calibrationoperation. The fourteenth embodiments can be modified to form additionalfourteenth embodiments in which the branch channel includes anaccumulator. The fourteenth embodiments can be modified to formadditional fourteenth embodiments in which the branch channel includesan accumulator with an internal volume in flow communication with thebranch channel, which internal volume size is selectable. The fourteenthembodiments can be modified to form additional fourteenth embodiments inwhich the branch channel includes an accumulator with an internal volumein flow communication with the branch channel, which internal volumesize is selectable under control of the controller.

According to fifteenth embodiments, the disclosed subject matterincludes a flow system with first and second peristaltic pumpsinterconnected in tandem by a channel with a component that permits anet flow into and out of the channel between the first and secondperistaltic pumps. The first and second peristaltic pumps has differentsized pumping tube segments engaged with respective rotors thereof suchthat when the first and second peristaltic pumps are pumpingapproximately equal flow rates, the frequency of flow and pressurefluctuations are substantially different.

The fifteenth embodiments can be modified to form additional fifteenthembodiments in which the component includes a dialyzer. The fifteenthembodiments can be modified to form additional fifteenth embodiments inwhich the fluid is incompressible. The fifteenth embodiments can bemodified to form additional fifteenth embodiments in which the first andsecond peristaltic pumps are interconnected by a fluid circuit thatlacks a pulsation damper.

According to sixteenth embodiments, the disclosed subject matterincludes a flow system with a fluid circuit with inflow and outflowchannels engageable, with respective peristaltic pumps, the inflow andoutflow channels is connected to a treatment device to provide ingoingand outcoming flow to and from the treatment device. The fluid circuithas valve portions that, upon actuation, connect a selected either oneof the inflow and outflow channels to a common segment. The commonsegment has pressure sensor elements on inlet and outlet ends thereof.

The sixteenth embodiments can be modified to form additional sixteenthembodiments in which a fluid management device with peristaltic pump andvalve actuators and a controller connected to the peristaltic pump andvalve actuators to control them, the peristaltic pump and valveactuators engaged with the inflow and outflow channels and valveportions respectively. The controller is connected to the pressuresensor elements, the controller further is programmed to maintain inflowand outflow rates to achieve a predefined ratio of net flow into or outof the treatment during a treatment interval responsively to correctionsderived from comparing pressure differences across sad pressure sensorsin ingoing and outgoing flows flowing through the common segment.

The sixteenth embodiments can be modified to form additional sixteenthembodiments in which the controller is programmed to switch the commonsegment between the ingoing flow and the outgoing flow periodicallyduring a treatment. The sixteenth embodiments can be modified to formadditional sixteenth embodiments in which the fluid circuit is adisposable component. The sixteenth embodiments can be modified to formadditional sixteenth embodiments in which the pressure sensor elementsare pressure pods entirely of plastic connectable to pressuretransducers which are in turn connected to the controller. The sixteenthembodiments can be modified to form additional sixteenth embodiments inwhich the common segment is of a material that has a lower compliancethan that of other portions of the fluid circuit.

According to seventeenth embodiments, the disclosed subject matterincludes a system for regulating balanced flow of fluids with a fluidcircuit with first and second fluid channels connectable to a fluidhandling device, each with at least one respective pump for each of thefirst and second fluid channels, a controller connected to therespective pumps to control the rate of pumping of one or more of therespective pumps, the controller is connected to one or more valves topermit it to establish flows in the first and second channels. A ratioof flow rates of entering and leaving flows to and from the fluidhandling device is controlled by the controller to effect a predefinednet transfer of fluid to or from the fluid handling device responsivelyto calibration data accessible to the controller. The controller, atselected times, temporarily establishes one or more calibration flowpaths in the fluid circuit, the calibration flow paths communicatingrespectively with ones of the first and second fluid channels to causeflow through a flow measurement component that generates a signalindicating a flow rate or relative flow rate generated by the respectivepumps. The controller samples the signal and in response to resultingsamples, the controller adjusting the calibration data. The controller,uses the adjusted calibration data stored in the controller to adjustthe one or more of the respective pumps in order to effect thepredefined net transfer of fluid to or from the fluid handling device.The selected times are determined by the controller responsively todetection of a number of rotations of one or more of the respectivepumps, a change in temperature of a portion of the fluid circuit, achange in pressure of a portion of the fluid circuit, a change in aconfiguration of the fluid circuit, an elapsed time since the fluidcircuit was set up, or an elapsed time that the fluid circuittransferred fluid was transferring fluid to and from the fluid handlingdevice.

The seventeenth embodiments can be modified to form additionalseventeenth embodiments in which the controller is connected to receivea local pressure upstream and/or downstream of at least one of therespective pumps, the adjusting is responsive to both the samples andthe local pressure signal. The seventeenth embodiments can be modifiedto form additional seventeenth embodiments in which the received localpressure includes local pressures upstream and downstream of the atleast one of the respective pumps. The seventeenth embodiments can bemodified to form additional seventeenth embodiments in which thecalibration flow paths include one through a test flow branch thatdirectly connects ones of the first and second fluid channels. Theseventeenth embodiments can be modified to form additional seventeenthembodiments in which the controller controls a valve that selectivelypermits flow through the test flow branch and the controllerautomatically iteratively establishes the continuous flow and theperformance of the sampling. The seventeenth embodiments can be modifiedto form additional seventeenth embodiments in which the fluid handlingdevice is a blood treatment device. The seventeenth embodiments can bemodified to form additional seventeenth embodiments in which the bloodtreatment device is a dialyzer or a hemofilter and replacement fluidsource. The seventeenth embodiments can be modified to form additionalseventeenth embodiments in which the respective pumps are peristalticpumps. The seventeenth embodiments can be modified to form additionalseventeenth embodiments in which the selected times are determined bythe controller responsively to detection of a number of rotations of oneor more of the respective pumps. The seventeenth embodiments can bemodified to form additional seventeenth embodiments in which theselected times are determined by the controller responsively todetection of a change in temperature of a portion of the fluid circuit.The seventeenth embodiments can be modified to form additionalseventeenth embodiments in which the selected times are determined bythe controller responsively to detection of a change in pressure of aportion of the fluid circuit. The seventeenth embodiments can bemodified to form additional seventeenth embodiments in which theselected times are determined by the controller responsively todetection of a change in a configuration of the fluid circuit. Theseventeenth embodiments can be modified to form additional seventeenthembodiments in which the selected times are determined by the controllerresponsively to detection of an elapsed time since the fluid circuit wasset up. The seventeenth embodiments can be modified to form additionalseventeenth embodiments in which the selected times are determined bythe controller responsively to detection of an elapsed time that thefluid circuit transferred fluid was transferring fluid to and from thefluid handling device.

According to eighteenth embodiments, the disclosed subject matterincludes a method of controlling a rate of ultrafiltration/infusion inan extracorporeal blood circuit with pumping treatment fluid throughblood treatment device using one or more peristaltic pumps. The methodincludes pumping blood through the blood treatment device using twopumps whose rates of flow are controlled by a controller to achieve apredefined volume of ultrafiltration by the end of a treatment interval.at times during a treatment, flowing blood between the two pumps andreceiving a pressure signal representative of the relative rates of flowbetween the two pumps. In the method, based on the pressure signal,calibration data is revised used to control the rates of flow to achievethe predefined volume.

The eighteenth embodiments can be modified to form additional eighteenthembodiments in which the two pumps are peristaltic pumps. The eighteenthembodiments can be modified to form additional eighteenth embodiments inwhich the receiving a pressure signal includes receiving a transientstatic pressure generated by unequal flows of the two pumps to and froma branch channel connecting the two pumps. The eighteenth embodimentscan be modified to form additional eighteenth embodiments in which therevising includes changing a pumping rate of one of the two pumpsresponsively to an average of the pressure signal to achieve anunchanging pressure and using data indicating the rotation rate of theone of the two pumps when the unchanging pressure is achieved to revisethe calibration data.

According to nineteenth embodiments, the disclosed subject matterincludes a system for regulating balanced flow of fluids with first andsecond fluid channels connectable to a fluid handling device, each withat least one respective pump for each of the first and second fluidchannels, a controller connected to the respective pumps to control therate of pumping of one or more of the respective pumps. The controlleris connected to one or more valves to permit it to establish flows inthe first and second channels. a ratio of flow rates of entering andleaving flows to and from the fluid handling device is controlled by thecontroller to effect a predefined net transfer of fluid to or from thefluid handling device responsively to calibration data accessible to thecontroller. The controller, at selected times, temporarily establishes abypass flow directly from the first channel to the second channel,thereby bypassing connectors to the fluid handling device, through atest flow branch by defining selected flow paths through the one or morevalves. The test flow branch has an accumulator with a volume that canbe changed under control of the controller, a pressure sensor device inthe test flow branch to measure a pressure of fluid in the accumulatorvolume, the controller is programmed to sample a signal from thepressure sensor device and in response to the samples, the controller isprogrammed to adjust one or both of the calibration data and theaccumulator volume. The controller is programmed to change the volume ofthe accumulator responsively to at least one flow condition in the testflow branch at the selected times. The controller, using the adjustedcalibration data stored in the controller, adjusts the one or more ofthe respective pumps in order to effect the predefined net transfer offluid to or from the fluid handling device at times other than theselected times.

The nineteenth embodiments can be modified to form additional nineteenthembodiments in which the controller is programmed to sample a signalfrom the pressure sensor device and in response to the samples, thecontroller adjusting the accumulator volume responsively to the pressureindicated by the pressure sensor device. The nineteenth embodiments canbe modified to form additional nineteenth embodiments in which the atleast one flow condition includes a flow rate through the test flowbranch. The nineteenth embodiments can be modified to form additionalnineteenth embodiments in which the controller is programmed to changethe volume to keep the pressure therein constant and to adjust thecalibration data responsively to the time-change of volume in theaccumulator. The nineteenth embodiments can be modified to formadditional nineteenth embodiments in which the controller is programmedto change the volume to keep the pressure therein constant and to adjustthe rate of at least one of the respective pumps to minimize change inthe volume in the accumulator. The nineteenth embodiments can bemodified to form additional nineteenth embodiments in which thecontroller is programmed to adjust the calibration data responsively tothe rate of rotation of the at least one of the respective pumps uponthe minimization of the change in the volume in the accumulator. Thenineteenth embodiments can be modified to form additional nineteenthembodiments in which the controller controls a valve that selectivelypermits flow through the test flow branch and the controllerautomatically selects a time of establishing the continuous flow andperforming the sampling.

According to twentieth embodiments, the disclosed subject matterincludes a medical treatment method according to which, at treatmenttimes and using peristaltic pumps, medicament is flowed into and out ofinflow and outflow channels connectable to a patient or treatmentdevice. At calibration times, over a calibration interval of less than aminute, medicament is directly flowed between the inflow and outflowchannels such that pulsations generated by the peristaltic pumps causethe pressure in a bridge channel between the inflow and outflow channelsto fluctuate due to a superposition of a suction side pulsation and apressure side pulsation of respective ones of the peristaltic pumps. Themethod includes, using an adjustable flow restrictor, selecting asuction head of at least one of the respective ones of the peristalticpumps so as to change the pulsation frequency thereof so that it differsfrom that of the other of the ones of the peristaltic pumps by apredetermined amount.

The twentieth embodiments can be modified to form additional twentiethembodiments in which the predetermined amount is such that the ratio ofthe inverse of the difference between the pulsation frequencies of theones of the peristaltic pumps is multiple times the calibrationinterval. The twentieth embodiments can be modified to form additionaltwentieth embodiments in which the predetermined amount is such that theratio of the inverse of the difference between the pulsation frequenciesof the ones of the peristaltic pumps is three times the calibrationinterval. The twentieth embodiments can be modified to form additionaltwentieth embodiments in which the predetermined amount is such that theratio of the inverse of the difference between the pulsation frequenciesof the ones of the peristaltic pumps is five times the calibrationinterval. The twentieth embodiments can be modified to form additionaltwentieth embodiments in which the predetermined amount is such that theratio of the inverse of the difference between the pulsation frequenciesof the ones of the peristaltic pumps is eight times the calibrationinterval. The twentieth embodiments can be modified to form additionaltwentieth embodiments in which the predetermined amount is such that theratio of the inverse of the difference between the pulsation frequenciesof the ones of the peristaltic pumps is twelve times the calibrationinterval.

According to twenty-first embodiments, the disclosed subject matterincludes a medical treatment system with a first fluid managementelement that pumps fluid from a patient interface device during atreatment. A second fluid management element pumps fluid into a patientinterface device during a treatment. The patient interface device is adevice that interfaces with a patient fluid compartment includes atleast one of a dialyzer, a hemofilter, a hemodiafilter, an ultrafilter,and a plasmapheresis device. A controller is connected to at least oneof the first and second fluid management elements and has a processorprogrammed to regulate a net transfer of fluid into or from the patientinterface device to achieve a predefined net removal of fluid from thepatient during a therapeutic treatment implemented under control of thecontroller. A fluid circuit switch allows a flow from at least one ofthe first and second fluid management elements to be selectively andautomatically configured under control of the controller between atherapy configuration for delivering the therapeutic treatment to acalibration configuration in which flow through the at least one of thefirst and second fluid management elements is temporarily diverted to aflow or pressure sensor that outputs a signal indicating a differencebetween the flow rates of the first and second fluid management elementsthat occurs during a treatment the fluid circuit is configured to returnfluid passing the flow or pressure sensor to a recovery channel that isconnected to permit a concurrent or later use of the fluid. Thecontroller is programmed to calculate and store flow correction datarepresenting a correction to be applied to a rate of flow of the atleast one of the first and second fluid management elements responsivelyto the signal. The controller is further programmed to modify a flowrate of the at least one of the first and second fluid managementelements responsively to the flow correction data.

The twenty-first embodiments can be modified to form additionaltwenty-first embodiments in which the fluid circuit is configured toreturn fluid passing the flow or pressure sensor to the at least one ofthe first and second fluid management elements. The twenty-firstembodiments can be modified to form additional twenty-first embodimentsin which the fluid circuit is configured to return fluid passing theflow or pressure sensor to a collection container connectable to the atleast one of the first and second fluid management elements. Thetwenty-first embodiments can be modified to form additional twenty-firstembodiments in which the fluid circuit is configured to return fluidpassing the flow or pressure sensor to a collection containerconnectable to a source fluid container connected to the first andsecond fluid management elements. The twenty-first embodiments can bemodified to form additional twenty-first embodiments in which a divertedflow in the calibration configuration flows between the first and secondfluid management elements through a fluid accumulator connected to apressure sensor that outputs the signal. The twenty-first embodimentscan be modified to form additional twenty-first embodiments in which theaccumulator is configured such that pressure increases as fluid fillsthe accumulator, whereby a difference in the flow rates of the first andsecond fluid management elements results in an increasing or decreasingpressure. The twenty-first embodiments can be modified to formadditional twenty-first embodiments in which the accumulator has aresidual volume of fluid to permit the measurement of a pressure changecaused by a net removal or a net addition of fluid from or to theaccumulator. The twenty-first embodiments can be modified to formadditional twenty-first embodiments in which wherein the first fluidmanagement element includes a peristaltic pump.

The twenty-first embodiments can be modified to form additionaltwenty-first embodiments in which the fluid circuit includes adisposable plastic tubing set and at least one control valve. Thecontrol valve includes a tubing junction that interfaces with one ormore pinch clamps to form selectable flow paths, the pinch clamps ispermanent reusable elements that pinch respective portions of the tubingset. The twenty-first embodiments can be modified to form additionaltwenty-first embodiments that include a third fluid management elementthat pumps fluid into the patient interface device during a treatment,the third fluid management element is coupled to a synchronizationmechanism that causes the first and third fluid management elements topump equal amounts of fluid per unit time during a treatment.

The twenty-first embodiments can be modified to form additionaltwenty-first embodiments that include a third fluid management elementthat pumps fluid into the patient interface device during a treatment.The third fluid management element is coupled to a mechanicalsynchronization mechanism that causes the first and third fluidmanagement elements to move such that they pump equal amounts of fluidper unit time during a treatment through the fluid circuit.

The twenty-first embodiments can be modified to form additionaltwenty-first embodiments that include a blood circuit that interfaceswith the patient interface device and, through the latter, to the fluidcircuit. The twenty-first embodiments can be modified to form additionaltwenty-first embodiments in which the flow or pressure sensor is a flowsensor. The twenty-first embodiments can be modified to form additionaltwenty-first embodiments that include a blood circuit that interfaceswith the patient interface device and, through the latter, to the fluidcircuit and wherein a diverted flow in the calibration configurationflows through a flow path between the first and second fluid managementelements through a fluid accumulator connected to a pressure sensor thatoutputs the signal, wherein a fluid circuit portion connected to thepatient interface device is separate from the flow path.

The twenty-first embodiments can be modified to form additionaltwenty-first embodiments in which the second fluid management element isconnected to a source of a medicament. The twenty-first embodiments canbe modified to form additional twenty-first embodiments in which thecontroller is connected to a user interface and programmed to accept andstore ultrafiltration data representing a target net ultrafiltration,wherein the controller is further programmed to control flow through theat least the one of the first and second fluid management elementsresponsively to the ultrafiltration data.

According to twenty-second embodiments, the disclosed subject matterincludes a method of controlling a balanced flow in a medical treatment.The method includes using at least two pumps, flowing fluid into and outof a fluid management component over the course of a treatment intervaland controlling the rates of flow of the at least two pumps to meet atarget net flow into or out of the fluid management component at an endof the treatment interval. at calibration times during the treatmentinterval, and interconnecting the at least two pumps and detecting aproperty resulting from a difference in the flow rates of the pumpsduring a calibration interval. The method further includes, in responseto the detecting, providing data to a controller that controls the ratesof flow of the pumps. the controller, in response to the data, modifyingthe rates of flow to meet the target net flow.

The twenty-second embodiments can be modified to form additionaltwenty-second embodiments in which the fluid management component is adialyzer. The twenty-second embodiments can be modified to formadditional twenty-second embodiments in which the fluid managementcomponent is a combination of a hemofilter and patient access. Thetwenty-second embodiments can be modified to form additionaltwenty-second embodiments in which the fluid management component is aperitoneum of a patient is treated with peritoneal dialysis. Thetwenty-second embodiments can be modified to form additionaltwenty-second embodiments in which the controller controls the rates ofthe pumps to compensate an error that accumulates during an entirety ofthe treatment interval. The twenty-second embodiments can be modified toform additional twenty-second embodiments in which the controllercontrols the rates of the pumps to compensate an error that accumulatesup to each instance of the calibration times.

According to twenty-third embodiments, the disclosed subject matterincludes a method of controlling a balanced flow in a medical treatment.The method includes using at least two pumps, flowing fluid into and outof a fluid management component over the course of a treatment intervaland controlling the rates of flow of the at least two pumps to meet atarget net flow into or out of the fluid management component at an endof the treatment interval. The method includes, at calibration timesduring the treatment interval, interconnecting the at least two pumpsand detecting a property resulting from a difference in the flow ratesof the pumps during a calibration interval. The method includes, inresponse to the detecting, providing data to a controller that controlsthe rates of flow of the pumps. The controller, in response to the data,modifies the rates of flow to meet the target net flow.

The twenty-third embodiments can be modified to form additionaltwenty-third embodiments in which the flow rates established at thecalibration times are varied and the detecting includes convolving asampled pressure signal with a window function whose temporal size isvaried with a flow rate of at least one of the at least two pumps. Thetwenty-third embodiments can be modified to form additional twenty-thirdembodiments in which the flow rates established at the calibration timesare varied and the detecting includes convolving a sampled pressuresignal with a window function whose shape is varied with a flow rate ofat least one of the at least two pumps. The twenty-third embodiments canbe modified to form additional twenty-third embodiments in which theflow rates established at the calibration times are varied and thedetecting includes convolving a sampled pressure signal with a windowfunction whose temporal size is varied with a characteristic of thesuperposition of pulsations in pressure caused by the at least twointerconnected pumps. The twenty-third embodiments can be modified toform additional twenty-third embodiments in which the fluid managementcomponent is a dialyzer. The twenty-third embodiments can be modified toform additional twenty-third embodiments in which the fluid managementcomponent is a combination of a hemofilter and patient access. Thetwenty-third embodiments can be modified to form additional twenty-thirdembodiments in which the fluid management component is a peritoneum of apatient is treated with peritoneal dialysis. The twenty-thirdembodiments can be modified to form additional twenty-third embodimentsin which the controller controls the rates of the pumps to compensate anerror that accumulates during an entirety of the treatment interval. Thecontroller controls the rates of the pumps to compensate an error thataccumulates up to each instance of the calibration times.

According to twenty-fourth embodiments, the disclosed subject matterincludes a medical treatment system that includes a first fluidmanagement element that pumps fluid from a patient interface deviceduring a treatment. A second fluid management element that pumps fluidinto a patient interface device during a treatment. The patientinterface device including at least one of a dialyzer, a hemofilter, ahemodiafilter, an ultrafilter, and a plasmapheresis device. A bloodcircuit that connects the patient interface device to a patient access.A controller connected to at least one of the first and second fluidmanagement elements and having a processor programmed to implement atreatment mode in which it selectively establishes a net flow differencebetween the first fluid management element and second fluid managementelement corresponding to a net transfer of fluid into or from thepatient interface device to achieve a predefined net removal of fluidfrom the patient by regulating rates of flow through said first andsecond fluid management elements. The controller being furtherconfigured to implement a calibration mode in prevents a net flowdifference between the first fluid management element and the secondfluid management element and simultaneously sample a flow or pressuresensor output, the sensor output indicating a difference between therespective flow rates through the first and second fluid managementelements. The controller being programmed to calculate and store flowcorrection data representing a correction to be applied to a rate offlow of said at least one of the first and second fluid managementelements responsively to samples of the flow or pressure sensor output.The controller being further programmed to modify a flow rate of said atleast one of the first and second fluid management elements responsivelyto said flow correction data.

The twenty-fourth embodiments can be modified to form additionaltwenty-fourth embodiments in which the flow or pressure sensor is apressure sensor. The twenty-fourth embodiments can be modified to formadditional twenty-fourth embodiments in which a flow during thecalibration configuration flows between the first and second fluidmanagement elements through a circuit portion that includes a fluidaccumulator connected to a pressure sensor that outputs said signal. Thetwenty-fourth embodiments can be modified to form additionaltwenty-fourth embodiments in which, in the calibration mode, pressureincreases or decreases in the first and second fluid management elementsin response to a difference between the flow rates of said first andsecond fluid management elements. The twenty-fourth embodiments can bemodified to form additional twenty-fourth embodiments in which theaccumulator has a residual volume of fluid to permit the measurement ofa pressure change caused by a net removal or a net addition of fluidfrom or to said accumulator. The twenty-fourth embodiments can bemodified to form additional twenty-fourth embodiments in which the firstfluid management element includes a peristaltic pump. The twenty-fourthembodiments can be modified to form additional twenty-fourth embodimentsin which the second fluid management element includes a peristalticpump. The twenty-fourth embodiments can be modified to form additionaltwenty-fourth embodiments in which the fluid circuit includes adisposable plastic tubing set and at least one control valve, thecontrol valve including a tubing junction that interfaces with one ormore pinch clamps to form selectable flow paths, the pinch clamps beingpermanent reusable elements that pinch respective portions of the tubingset.

The twenty-fourth embodiments can be modified to form additionaltwenty-fourth embodiments in which the system further comprises a thirdfluid management element that pumps fluid into the patient interfacedevice during a treatment, the third fluid management element beingcoupled to a synchronization mechanism that causes the first and thirdfluid management elements to pump equal amounts of fluid per unit timeduring a treatment. The twenty-fourth embodiments can be modified toform additional twenty-fourth embodiments in which the system furthercomprises a third fluid management element that pumps fluid into thepatient interface device during a treatment, the third fluid managementelement being coupled to a synchronization mechanism that causes thefirst and third fluid management elements to pump equal amounts of fluidper unit time during a treatment. The twenty-fourth embodiments can bemodified to form additional twenty-fourth embodiments in which thesystem further comprises a blood circuit that interfaces with thepatient interface device and, through the latter, to the fluid circuitand wherein a diverted flow in the calibration configuration flowsthrough a flow path between the first and second fluid managementelements through a fluid accumulator connected to a pressure sensor thatoutputs said signal, wherein a fluid circuit portion connected to thepatient interface device is separate from said flow path. Thetwenty-fourth embodiments can be modified to form additionaltwenty-fourth embodiments in which the controller is connected to a userinterface and programmed to accept and store ultrafiltration datarepresenting a target net ultrafiltration, wherein the controller isfurther programmed to control flow through said at least said one ofsaid first and second fluid management elements responsively to saidultrafiltration data.

According to twenty-fifth embodiments, the disclosed subject matterincludes a medical treatment system including a first pump that pumpsfluid from a patient interface device during a treatment. A second pumpthat pumps fluid into a patient interface device during a treatment. Thepatient interface device being a device that interfaces with a patientfluid compartment including at least one of a dialyzer, a hemofilter, ahemodiafilter, an ultrafilter, and a plasmapheresis device. A controllerconnected to at least one of the first and second fluid managementelements and having a processor programmed to regulate a net transfer offluid into or from the patient interface device to achieve a predefinednet removal of fluid from the patient during a therapeutic treatmentimplemented under control of the controller by regulating difference inthe flow between the first pump and the second pump. A fluid circuitswitch that allows a flow from the at least one of the first and secondpumps to be selectively and automatically configured under control ofthe controller between a therapy configuration for delivering saidtherapeutic treatment to a calibration configuration in which an averageflow difference between the flow in the first pump and the flow in thesecond pump is temporarily prevented and a flow or pressure sensor thatoutputs a signal indicating an instantaneous difference between the flowrates of the first and second pumps that occurs during a treatment. Thecontroller being programmed to calculate and store flow correction datarepresenting a correction to be applied to a rate of flow of said atleast one of the first and second pumps responsively to said signal. Thecontroller being further programmed to modify a flow rate of at leastone of the first and second pumps responsively to said flow correctiondata.

The twenty-fifth embodiments can be modified to form additionaltwenty-fifth embodiments in which a diverted flow in the calibrationconfiguration flows between the first and second pumps through a fluidaccumulator connected to a pressure sensor that outputs said signal. Thetwenty-fifth embodiments can be modified to form additional twenty-fifthembodiments in which a diverted flow in the calibration configurationflows between the first and second pumps through a pressure sensor thatoutputs said signal. The twenty-fifth embodiments can be modified toform additional twenty-fifth embodiments in which the accumulator isconfigured such that pressure registered by said pressure sensor as dueto a difference in the flow rates of said first and second pumps. Thetwenty-fifth embodiments can be modified to form additional twenty-fifthembodiments in which the first and/or second pump includes a peristalticpump.

According to twenty-sixth embodiments, the disclosed subject matterincludes a medical treatment system including a controller and controlvalve actuators and first and second pumps, the control valve actuatorsand pumps being controlled by said controller. The first pump beingcontrolled to regulate flow toward a patient interface device and thesecond pump a being controlled to regulate flow from the same patientinterface device. The patient interface device being a device that isseparate from the claimed treatment system that interfaces with apatient fluid compartment including at least one of a dialyzer, ahemofilter, a hemodiafilter, an ultrafilter, and a plasmapheresisdevice. The controller including a processor programmed to regulate thespeed of the first and second pumps to achieve a predefined net removalof fluid from the patient interface device during a treatment interval.The processing being further programmed to control the control valveactuators to switch between a first position that configures a fluidcircuit, when attached to said control valves, in a bypass configurationwhich defines a bypass flow path that directly connects the first andsecond pumps such that a net flow from or into said bypass flow path isprevented as otherwise exists during the treatment. A pressuretransducer connected to convey pressure signals to the controller, thepressure signals indicating pressure in the bypass flow path. Thecontroller being programmed to calculate and store flow correction datarepresenting a correction to be applied to a rate of flow of said atleast one of the first and second pumps responsively to said signal. Thecontroller being further programmed to modify a flow rate of said atleast one of the first and second pumps responsively to said flowcorrection data.

The twenty-sixth embodiments can be modified to form additionaltwenty-sixth embodiments in which a flow in the bypass configurationflows between the first and second pumps through a fluid accumulatorconnected to a pressure sensor that outputs said signal. Thetwenty-sixth embodiments can be modified to form additional twenty-sixthembodiments in which the bypass flow path is such that pressureincreases or decreases therein depending on an instantaneous differencein the flow rates of said first and second pumps. The twenty-sixthembodiments can be modified to form additional twenty-sixth embodimentsin which the first and/or second pump includes a peristaltic pump.

According to twenty-seventh embodiments, the disclosed subject matterincludes a method of regulating the balanced flow of fluids. The methodincludes, in a system having first and second fluid channels each withat least one respective pump for each of said first and second fluidchannels, using a controller to control the rate of pumping of one ormore of said respective pumps to establish flows in the first and secondchannels of equal volume flow rate based on calibration data stored insaid controller. The method includes the first and second channelsconnecting to a fluid handling device in which a ratio of flow rates ofentering and leaving flows to and from said fluid handling device ismaintained by said controller. The method includes using the controller,temporarily establishing a calibration flow from said first channel tosaid second channel such that a measurable pressure change is indicatedby a calibration pressure sensor in said calibration flow when adifference in flow rates of said respective pumps exists. The methodincludes, in response to said calibration pressure signal, using thecontroller, adjusting said calibration data. The method includes,thereafter, using said controller, adjusting one or more of saidrespective pumps according to the calibration data adjusted by saidadjusting.

The twenty-seventh embodiments can be modified to form additionaltwenty-seventh embodiments in which said controller receives a localpressure upstream and/or downstream of at least one of said respectivepumps, said adjusting being responsive to both of said calibrationpressure signal and said local pressure signal. The twenty-seventhembodiments can be modified to form additional twenty-seventhembodiments in which said receiving a local pressure includes receivinglocal pressures upstream and downstream of said at least one of saidrespective pumps. The twenty-seventh embodiments can be modified to formadditional twenty-seventh embodiments in which the controller controls avalve that selectively defines said calibration flow by routing flowthrough a predefined flow branch and said controller automaticallyselects a time of said temporarily establishing. The twenty-seventhembodiments can be modified to form additional twenty-seventhembodiments in which the fluid handling device is a blood treatmentdevice. The twenty-seventh embodiments can be modified to formadditional twenty-seventh embodiments in which the blood treatmentdevice is a dialyzer or a hemofilter and replacement fluid source. Thetwenty-seventh embodiments can be modified to form additionaltwenty-seventh embodiments in which the respective pumps are peristalticpumps.

Embodiments (which include the claims) refer to the generalization of a“patient interface device.” This term designates any device thattransfer fluid to or from a patient fluid such as blood or plasma oreven an exogenous source of blood or patient body fluid which may bediluted or dehydrated by fluid exchange. Examples include a dialyzer, ahemofilter, a hemodiafilter, an ultrafilter, and a plasmapheresisdevice. It is noted that a hemofilter, for example, may further includean infusion port which provides the fluid inflow to a patient, an excessof which may tend to cause dilution and a single waste port of ahemofilter, an excess of flow through which may tend to causedehydration. Thus, a patient interface device of a hemofiltration systemmay be said to include the filter and the infusion port. Any of theembodiments may be modified according to this general definition ofpatient interface device or any examples of such devices. For example,these may include devices that achieve separation of one fluid that mustbe balanced and other components, such as a centrifuge.

Note that as the term is used herein, “balanced” flow may refer to equalflows or flows that differ by a predefined amount, for example toaccount for ultrafiltration. During calibrations, balanced flows mayhave a zero differential, however, an arbitrary predefined offset fromequal flows may still permit calibration, as should be clear to theskilled practitioner, and may be used to form variants, any of which iswithin the scope of the present disclosure.

It will be appreciated that the controllers, processes, systems, andsections described above can be implemented in hardware, hardwareprogrammed by software, software instruction stored on a non-transitorycomputer readable medium or a combination of the above. For example, amethod for balancing fluid flow can be implemented, for example, using aprocessor configured to execute a sequence of programmed instructionsstored on a non-transitory computer readable medium. For example, theprocessor can include, but not be limited to, a personal computer orworkstation or other such computing system that includes a processor,microprocessor, microcontroller device, or is comprised of control logicincluding integrated circuits such as, for example, an ApplicationSpecific Integrated Circuit (ASIC). The instructions can be compiledfrom source code instructions provided in accordance with a programminglanguage such as Java, C++, C#.net or the like. The instructions canalso comprise code and data objects provided in accordance with, forexample, the Visual Basic™ language, LabVIEW, or another structured orobject-oriented programming language. The sequence of programmedinstructions and data associated therewith can be stored in anon-transitory computer-readable medium such as a computer memory orstorage device which may be any suitable memory apparatus, such as, butnot limited to read-only memory (ROM), programmable read-only memory(PROM), electrically erasable programmable read-only memory (EEPROM),random-access memory (RAM), flash memory, disk drive and the like.

Furthermore, the modules, processes, systems, and sections can beimplemented as a single processor or as a distributed processor.Further, it should be appreciated that the steps mentioned above may beperformed on a single or distributed processor (single and/ormulti-core). Also, the processes, modules, and sub-modules described inthe various figures of and for embodiments above may be distributedacross multiple computers or systems or may be co-located in a singleprocessor or system. Exemplary structural embodiment alternativessuitable for implementing the modules, sections, systems, means, orprocesses described herein are provided below.

The modules, processors or systems described above can be implemented asa programmed general purpose computer, an electronic device programmedwith microcode, a hard-wired analog logic circuit, software stored on acomputer-readable medium or signal, an optical computing device, anetworked system of electronic and/or optical devices, a special purposecomputing device, an integrated circuit device, a semiconductor chip,and a software module or object stored on a computer-readable medium orsignal, for example.

Embodiments of the method and system (or their sub-components ormodules), may be implemented on a general-purpose computer, aspecial-purpose computer, a programmed microprocessor or microcontrollerand peripheral integrated circuit element, an ASIC or other integratedcircuit, a digital signal processor, a hardwired electronic or logiccircuit such as a discrete element circuit, a programmed logic circuitsuch as a programmable logic device (PLD), programmable logic array(PLA), field-programmable gate array (FPGA), programmable array logic(PAL) device, or the like. In general, any process capable ofimplementing the functions or steps described herein can be used toimplement embodiments of the method, system, or a computer programproduct (software program stored on a non-transitory computer readablemedium).

Furthermore, embodiments of the disclosed method, system, and computerprogram product may be readily implemented, fully or partially, insoftware using, for example, object or object-oriented softwaredevelopment environments that provide portable source code that can beused on a variety of computer platforms. Alternatively, embodiments ofthe disclosed method, system, and computer program product can beimplemented partially or fully in hardware using, for example, standardlogic circuits or a very-large-scale integration (VLSI) design. Otherhardware or software can be used to implement embodiments depending onthe speed and/or efficiency requirements of the systems, the particularfunction, and/or particular software or hardware system, microprocessor,or microcomputer being utilized. Embodiments of the method, system, andcomputer program product can be implemented in hardware and/or softwareusing any known or later developed systems or structures, devices and/orsoftware by those of ordinary skill in the applicable art from thefunction description provided herein and with a general basic knowledgeof controllers and especially digital controllers and/or computerprogramming arts.

Moreover, embodiments of the disclosed method, system, and computerprogram product can be implemented in software executed on a programmedgeneral purpose computer, a special purpose computer, a microprocessor,or the like.

It is, thus, apparent that there is provided, in accordance with thepresent disclosure, flow balancing devices, methods and systems. Manyalternatives, modifications, and variations are enabled by the presentdisclosure. Features of the disclosed embodiments can be combined,rearranged, omitted, etc., within the scope of the invention to produceadditional embodiments. Furthermore, certain features may sometimes beused to advantage without a corresponding use of other features.Accordingly, Applicants intend to embrace all such alternatives,modifications, equivalents, and variations that are within the spiritand scope of the present invention.

The invention claimed is:
 1. A flow balancing system for a bloodtreatment device, comprising: one or more inflow pumps and one or moreoutflow pumps positioned to engage a replaceable fluid circuit to pumpfluid into and out of the blood treatment device, respectively; at leastone adjustable flow-restricting actuator configured to generate a flowrestriction of a selected magnitude in at least one portion of thereplaceable fluid circuit, the at least one adjustable flow-restrictingactuator located at an inlet of a respective one of said one or moreinflow pumps and one or more outflow pumps to generate a selectablesuction head during pumping; valve actuators that control valve portionsof the replaceable fluid circuit; a controller connected to said one ormore inflow and outflow pumps and configured to control speeds thereof,configured to control said valve actuators, and configured to controlsaid at least one adjustable flow-restricting actuator; the controllerhaving a data store storing a model that predicts data indicative of aflow rate based on at least one of pump speed and inlet and/or outletpressure of each of said one or more inflow and outflow pumps; thereplaceable fluid circuit having at least an inflow channel, an outflowchannel, and a branch channel, the inflow channel and the outflowchannel connecting to the blood treatment device, the inflow channel andthe outflow channel being connected to the branch channel such that theinflow and outflow channels can be bridged by the valve actuators tocause fluid flowing in the inflow channel to bypass the blood treatmentdevice and to flow from the inflow channel through the branch channel tothe outflow channel; the branch channel including an accumulator with aninternal volume that is selectable in flow communication with the branchchannel; one or more pressure sensors interoperable with the branchchannel and configured to detect pressure at a respective one or morepoints along the branch channel; the controller being programmed togenerate a test command and in response thereto, perform a calibrationoperation during which it bridges the inflow and outflow channelsthrough said branch channel and to calculate a difference in flow ratesbetween the one or more inflow pumps and the one or outflow pumpsthrough said branch channel and, responsively thereto, to calculateadjustments to the model; and the controller being programmed to controlthe one or more inflow and outflow pumps responsively to the model. 2.The system of claim 1, wherein the difference in flow rates between theone or more inflow pumps and the one or more outflow pumps through saidbranch channel is calculated from pressure signals indicating a pressuredrop in the branch channel.
 3. The system of claim 1, wherein thedifference in flow rates between the one or more inflow pumps and theone or more outflow pumps through said branch channel is calculated froma single pressure signal indicating a net inflow or net outflow from thebranch channel.
 4. The system of claim 1, wherein the controller isprogrammed to generate the test command upon the detection of apredefined operating time interval of one of the one or more inflow andoutflow pumps.
 5. The system of claim 1, wherein the controller isprogrammed to generate the test command upon the detection of apredefined number of rotations of the one or more inflow and outflowpumps.
 6. The system of claim 1, wherein the controller is programmed togenerate the test command upon the detection of a predefined net flowvolume derived numerically from a number of rotations of the one or moreinflow and outflow pumps.
 7. The system of claim 1, wherein thecontroller is programmed to adjust the at least one adjustableflow-restricting actuator to generate an inlet pressure of one of theone or more inflow and outflow pumps during the calibration operation.8. The system of claim 1, wherein the controller is programmed to adjustthe at least one adjustable flow-restricting actuator to generate afirst inlet pressure at one of the one or more inflow and outflow pumpsduring the calibration operation matching a second inlet pressureoccurring during a treatment operation.
 9. The system of claim 1,wherein the controller is programmed to adjust the at least oneadjustable flow-restricting actuator to generate multiple first inletpressures at one of the one or more inflow and outflow pumps during thecalibration operation.
 10. The system of claim 9, wherein the differencein flow rates between the one or more inflow pumps and the one or moreoutflow pumps through said branch channel is calculated from pressuresignals indicating a pressure drop in the branch channel.
 11. The systemof claim 9, where in the difference in flow rates between the one ormore inflow pumps and the one or more outflow pumps through said branchchannel is calculated from a single pressure signal indicating a netinflow or net outflow from the branch channel.
 12. The system of claim9, wherein the controller is programmed to generate the test commandupon the detection of a predefined operating time interval of one of theone or more inflow and outflow pumps.
 13. The system of claim 9, whereinthe controller is programmed to generate the test command upon thedetection of a predefined number of rotations of the one or more inflowand outflow pumps.
 14. The system of claim 9, wherein the controller isprogrammed to generate the test command upon the detection of apredefined net flow volume derived numerically from a number ofrotations of the one or more inflow and outflow pumps.
 15. The system ofclaim 9, wherein the controller is programmed to adjust the at least oneadjustable flow-restricting actuator to generate an inlet pressure ofone of the one or more inflow and outflow pumps during the calibrationoperation.
 16. The system of claim 1, wherein the controller isprogrammed to generate the test command upon the detection of apredefined temperature of the replaceable fluid circuit.
 17. The systemof claim 1, wherein the controller is programmed to generate the testcommand upon the detection of a predefined temperature or temperaturechange of the replaceable fluid circuit.
 18. The system of claim 1,wherein the controller is programmed to generate the test command uponthe detection of a predefined pressure or pressure change of at alocation in the replaceable fluid circuit.
 19. The system of claim 1,wherein the controller is programmed to control said valve actuators torecover fluid flowing through the branch channel for use in a treatment.20. The system of claim 9, wherein the replaceable fluid circuitincludes a storage vessel in communication with the outflow channel andthe inflow channel and the controller is configured to direct fluidflowing through the branch channel to said storage vessel and from thestorage vessel to the inflow channel during a treatment, whereby fluidflowing in said branch channel is recovered for use during treatment.21. The system of claim 1, wherein the controller calculates adifference in flow rates between the one or more inflow pumps and theone or more outflow pumps through said branch channel responsively to amoving time-average pressure drop or pressure generated from anon-rectangular averaging window.
 22. The system of claim 1, wherein thecontroller calculates a difference in flow rates between the one or moreinflow pumps and the one or more outflow pumps through said branchchannel responsively to a moving time-average pressure drop or pressuregenerated from a non-rectangular averaging window whose temporal lengthis greater than a wavelength of flow pulses caused by the one or moreinflow and outflow pumps flowing fluid through the branch channel. 23.The system of claim 1, wherein the branch channel includes anaccumulator.
 24. The system of claim 1, wherein the controller isprogrammed to adjust the flow rate of the one or more inflow and outflowpumps to generate multiple flow rates through the branch channel duringthe calibration operation.
 25. The system of claim 24, wherein thecontroller is programmed to adjust the at least one adjustableflow-restricting actuator to generate multiple first inlet pressures atone of the one or more inflow and outflow pumps during the calibrationoperation.